An example of successful scientific collaboration between Pakistan and Kazakhstan 9786012476323

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AL-FARABI KAZAKH NATIONAL UNIVERSITY

WORKING TOGETHER

Zh. A. Abilov and M. Iqbal Choudhary

AN EXAMPLE OF SUCCESSFUL SCIENTIFIC COLLABORATION BETWEEN PAKISTAN AND KAZAKHSTAN Inter-Islamic Scientic Cooperation Supported by the COMSTECH

lmaty «Kazakh University» 2012

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C 547:001.83(574+549.1)

Zh. A. Abilov and M. Iqbal Choudhary An example of successful scientific collaboration between Pakistan and Kazakhstan. – Almaty: Kazakh University, 2012 . – P. 142 + 12 p.Ph. ISBN 978–601–247–632–3 This book is dedicated to collaborative work between the scientists of International Center for Chemical Sciences (H.E.J. Research Institute of Chemistry Dr. Panjwani Center for Molecular Medicine and Drug Research) and Al-Farabi Kazakh National University under the Scientific Collaboration Protocol funded by the Ministry of Science and Technology, Government of Pakistan and Ministry of Education and Science, Republic of Kazakhstan. This book includes results of the collaborative work conducted in the field of organic chemistry, pharmacology and chemistry of natural compounds and polymers. Intended for undergraduate, graduate and PhD students specializing in field of organic chemistry, pharmacology and chemistry of natural compounds and polymers.

UDC 547:001.83(574+549.1)

© Abilov Zh. A., Choudhary M. Iqbal, 2012 ISBN 978–601–247–632–3

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© Al-Farabi Kazakh National University, 2012

ONTENT Foreword ................................................................................................................. 5 Abstract – English .................................................................................................. 9 Abstract– Russian ................................................................................................... 10 Introduction ............................................................................................................ 11 Scientic Visits (Pakistan) .................................................................................... 12 Scientic Visits (Kazakhstan) ................................................................................ 16 Training of Young Scholars .................................................................................. 20 RESEARCH PROJECTS PAK-KAZAKH SCIENTIFIC COLLABORATION PROJECT ENTITLED, “STUDIES on the BIOLOGICALLY ACTIVE METABOLITES from the PLANTS of CENTRAL ASIA” N. A. Sultanova, M. Iqbal Choudhary, T. Makhmoor, V. B. Omurkamzinova, Aa-ur-Rahman, and Z. A. Abilov Chemical investigation of genus Tamarix – T. hispida, T. ramosissima ...... 24 A.F. Miftahova, V. U. Ahmad, G. S. Burasheva, and Z. A. Abilov Biological Active Compounds from Halostachys caspica, Halocnenum strobilaceum, Suaeda physophora and Suaeda microphylla .......................... 36 F. Miftahova, A. Dar, A. U.Vikar, G. S. Burasheva, and Z. A. Abilov Bioassay of Extracts from Halocnemum strobilaceum, Suaeda Physophora, Suaeda microphylla and Halostachys caspica ................................................. 48 L. Korulkina, G. E. Zhusupova, Z. A. Abilov and M. Iqbal Choudhary Biologically Active Compounds from genus Limonium Mill ...................... 50 R. A. Muzichkina, Y. A. Litvinenko, M. Iqbal Choudhary and T. Makhmoor Method of Obtaining of Polyphenol Complex with Antioxidant Activity...... 55 B. K. Yeskaliyeva, G. S. Burasheva., M. Iqbal. Choudhary and Z. A. Abilov Saponins and Flavonoids from Aerial Parts of genus Climacoptera ........... 57 A. K.Umbetova, N. A. Sultanova, V .B. Omurkamzinova, M. Iqbal Choudhary and Z. A. Abilov Chemical Research of Kazakhstan euhalophyte species C. monspeliacum of Camphorosma genus and T. laxa, T. elongata of Tamarix genus of Chenopodiaceae, Tamaricaceae families ........................................................... 63 Z. Z. Karzhaubekova., B. S. Siddiqui, G. S. Burasheva and N. A. Sultanova Triterpenoids from the Aerial Parts of Kalidium ............................................ 74

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B. S. Siddiquia, K. Z. Butabayeva, G. S. Burasheva, D. Y.Korul’kin, S. K.Alia and H. A. Bhattia A new lignane and a new sesquiterpene from Eurotia ceratoides (L.) ........ 85 B. M. Kudaibergenova, S. U. Simjee , M. K. Beisebekov, M. Iqbal Choudhary and Z. A. Abilov A New Polymer Composite for In Vivo Drug Delivery .................................. 91 Z. Mynbayeva, M. Iqbal Choudhary and Z. A. Abilov Biologically Active Compounds of some Plants of Types: Tamarix and Reaumuria ............................................................................................................... 105 R. S. Iminova, A. Dar, M. K Beisebekov and Z. A. Abilov Immobilization of Drugs on Polymer-Clay Composition Carriers.............. 108 M. Z. Turmukhanova and M. Iqbal Choudhary Synthesis of phenylacetylenic derivatives of decahydroquinoline ............ 117 Research Publications ............................................................................................ 133 Patents ...................................................................................................................... 139 Future Prospects ..................................................................................................... 140 Pakistan-Kazakhstan Cooperation in Photographs ........................................... 141

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FOREWORD The international cooperation is one of the priorities of the Al-Farabi Kazakh National University as an indispensable part of integration into the global educational and scientic community as an important tool in ensuring a high quality education and scientic research conducted in accordance with international requirements. One of the important tasks of the Al-Farabi Kazakh National University in the eld of international relations is the development and consolidation of cooperation with leading foreign universities and research centers. Currently, Kazakhstan has created all necessary conditions for such cooperation through international agreements. Diverse in form and content of scientic communications of the Al-Farabi Kazakh National University in the framework of these agreements are carried out with a number of foreign research institutions and universities in the U.S., UK, Germany, Austria, France, Finland, China, India, Pakistan, Poland, the Czech Republic, Slovakia, etc. Through these relationships implementing joint research projects and research programs, symposiums and conferences, workshops and consultations, exchange of scientists, Doctors, Masters and students, which then have the opportunity to work on the most modern scientic equipment. A striking example of long-term and eective international cooperation is the collaboration of Al-Farabi Kazakh National University with the H.E.J. Research Institute of Chemistry Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi (Pakistan), which is implemented within the framework of scientic and technological cooperation between the Ministry of Education and Science of the Republic of Kazakhstan and the Ministry of Science and Technology of Pakistan. The program, in particular, provides for joint work aimed at solving a wide range of scientic, technological and technical problems in the eld of synthetic organic substances, natural compounds and pharmacology. The most important results of these studies are related to the problem 5

of expanding the range of novel domestic herbal remedies with a wide spectrum of therapeutic action, as a wild plant ora of Kazakhstan is available for self-renewable raw material source of high performance, not cumulative and don`t cause allergic reactions, drugs not only for medicine, but also for the veterinary and agriculture. As a part of Kazakhstan-Pakistani cooperation these research have gained impetus, their potentials are signicantly increased and reached the international level. The basic most signicant publications by the results of scientic cooperation of Al-Farabi Kazakh National University and H.E.J. Research Institute of Chemistry Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi in the area of natural compounds, organic chemistry and polymers are collected in the present book. We wish to express a condence that such a fruitful international cooperation will eectively continue and the results will make an outstanding contribution to the development of not only the chemistry of synthetic organic substances, natural compounds and pharmacology, but also Kazakhstan science in general, which will undoubtedly help to ease her to the forefront of the world.

Academic NAS RK G.M.Mutanov Rector of Al-Farabi Kazakh National University

It was the cold winter of Almaty in 1999 when we met many warmhearted Kazakh scientists. I was heading a delegation of Pakistani scientists to the newly born nation of Kazakhstan with the mission to develop active collaboration in various elds of science and technology between the two countries. Here we visited the faculty of chemical sciences of Al Faribi Kazak National University in its century old historical building in Almaty city and met with many senior and junior researchers. Among them was a relatively young man Prof. Dr. Zh. Abilov, who impressed me the most. His passion for scientic research, deep knowledge and willingness to act, and act quickly, highly impressed me. These were the kind of people we were looking for to build linkages between two brotherly Muslim nations. I asked my younger colleague Dr. M. Iqbal Choudhary to capture the essence of that moment and strive to build the much needed collaboration between the two countries. Time proved me right regarding my initial enthusiasm about him. Today I look back and cherish that dening moment of the rst ever visit of Pakistani researchers to Kazakhstan and draw satisfaction on the fact that these two groups are still actively engaged in scientic collaboration. In fact this collaboration has expanded in its magnitude as many more researchers came on board and a variety of research projects are being conducted. Pakistan-Kazakhstan collaboration in chemical sciences is an example of immense success, given the fact that only limited support was available for joint activities. Dozens of good quality research publications, international and national patents, monographs, research theses and most importantly a large group of younger scientists trained in two countries are undeniable proof of the immense success of this bilateral collaboration. This year as we celebrate the 12th anniversary of scientic collaboration, I wish to express my heartiest greetings to Prof. Dr. Z. Abilov, Prof. Dr. M. Iqbal Choudhary and their colleagues, counterparts and young researchers for making this collaboration a great success. As a maer of 7

fact, collaboration in the eld of chemical sciences believer us is the most successful among all other elds. I wish and pray that with time, this collaboration as well as personal bonds between the scientists of our two countries further grow and become a model for others to follow.

PROF. DR. ATTA-UR-RAHMAN, FRS Coordinator General COMSTECH Constitution Avenue, Islamabad

ABSTRACT This book is dedicated to 12 years of collaborative work between the scientists of International Center for Chemical Sciences (H.E.J. Research Institute of Chemistry Dr. Panjwani Center for Molecular Medicine and Drug Research) and Al-Farabi Kazakh National University under the Scientic Collaboration Protocol funded by the Ministry of Science and Technology, Government of Pakistan and Ministry of Education and Science, Republic of Kazakhstan. Under this project, three Professors, one Associate Professor, and ten young scientists from the Al-Farabi Kazakh National University (Almaty) have visited Pakistan. This book includes results of the collaborative work conducted in the eld of organic chemistry, pharmacology and chemistry of natural compounds and polymers. From Kazakh medicinal plants 300 biological by active compounds were isolated, some of them were new and many possess interesting biological activities. Many of these plant extracts and individual compounds were evaluated for their antibacterial, antifungal, antioxidant, antiamnezia, antidiabetic, growth-regulating, immunomodulatory, cytotoxic, toxicity (Brine Shrimp activity), e.t.c., activities. Immobilization of phytoremedies and drugs on composition polymer carriers was also investigated as a vehicle for drug delivery. Results of collaborative scientific work were published in 53 research publications in the top international journals, such as Tetrahedron Fitoterapia, Phytochemistry, Planta Medica, Journal of Ethnopharmocology, Chemistry of natural compounds, Helvetica Acta, Chemical and Pharmceutical Bulleten, Journal of Applied Chemistry, etc., other publications include, book of Abstracts of some International Conferences and Symposia as well as 9 patents successfully filed and obtained in Republic of Kazakhstan. Most importantly, this long standing collaboration, has helped us to learn from each other’s experiences and to train young scholars in the cutting edge technologies. As we look back, these 12 years of joint efforts in the field of chemical science give us satisfaction and motivate us to work together. The profound understanding of similarities in Kazakh and Pakistani cultures and personal friendship are the other two important outcomes of this joint pursuit of knowledge. 9





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INTRODUCTION One of the main objectives of the pharmaceutical program is to provide safe, eective and aordable medicines to the masses for the treatment of dierent diseases. Kazakhstan is rich in medicinally important ora and unbroken traditions of the use of herbal formulations, which can be used for the preparations of medicines. In current times, the development of phytopharmaceuticals from medicinal plants which have proven biological activities and safe prole are extremely desirable locally and internationally. It means that, development of the new pharmaceutical products from plants is one of the important objective in the eld of natural, product chemistry. In the year 1998, the Pak- Kazakh project Scientic Collaboration Protocol between Academy of Sciences of the Republic Kazakhstan and Ministry of Science and Technology Government of Pakistan in the eld of organic chemistry and chemistry of natural compounds was signed. During this project we studied biologically active compounds and bioaasay of some original species of genus Shueda, Tamarix, Climacoptera, Kalidium, Camforosma, Limonium, etc. Immobilization of phytoremedies and drugs on composition as polymer carriers has been given as well. This collaborative work brings together scientists of both countries to open up possibilities of engaging in meaningful collaborations between the two countries at international levels and will encourage the entire generation of young natural product chemists. Results of collaborative scientic work were published in many International journals and led 7 Ph.D. and 3 doctoral thesis.

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SCIENTIFIC VISITS (PAKISTAN) PROF. DR. ATTA-UR –RAHMAN, FRS Former Minister of Science Technology and Information Technology Nishan-e-Imtiaz, Hilal-e-Imtiaz, Sitara-eImtiaz, Tamgha-e-Imtiaz, Chief-Patron, ICCBS, HEC Distinguished National Professor, Sc.D. (Cantab), Hon. D.E.d. (Coventry), D.Sc. (AIT), D.Sc (Karachi), D.Sc. (Gomal), D.Sc. (UiTM, Malysia) Ph.D. (Organic Chemistry, Cambridge, UK), UNESCO Science Laureate, Khwarizmi Laureate, Austrian Award, Vice President (TWAS), Coordinator General COMSTECH, President Pakistan Academy of Sciences. He has 856 publications in several elds of organic chemistry including 665 research publications, 22 patents, 113 books and 65 chapters in books published largely by major U.S. and European presses. PROF. DR. M. IQBAL CHOUDHARY Director (H. E. J. Research Institute of Chemistry Dr. Panjwani Center for Molecular Medicine and Drug Research) Hilal-e-Imtiaz, Sitara-e-Imtiaz, Tamgha-eImtiaz, Director (ICCBS), Author / Editor of 24 books, 20 of which have been published in USA and Europe. Author of over 710 research publications, all published in USA, Europe, and Japan (Total Impact Factor 1,370), Highest number of international research papers in the country in last ten years (3% of total research publications in all disciplines), Highest number of citations (5,500) in last 5 years, COMSTECH Award inChemistry (2010) by the Prime Minister of Pakistan (2010), Khwarizmi International Award and Prize from the President of Islamic Republic of Iran (2006), 12

Economic Cooperation Organization (ECO) Award in Education 2006 by the President of Azerbaijan, Doctor of Science (D.Sc.) University of Karachi (2005), Distinguished National Professor of the Higher Education Commission (2004), Prof. Abdus Salam (Nobel Laureate) Prize in Chemistry (1989), Prof. Raziuddin Siddiqui Gold Medal of Pakistan Academy of Sciences (1992), Third World Academy of Science Young (Trieste Italy) Scientists Award (1994), National Book Foundation Prize (1995), Visiting Professor at the University of Rhode Island, USA,Visiting Professor at the King Saud University (KSU), Riyadh, Saudi Arabia, Visiting Professor at the Universiti Teknologi MARA (UiTM), Malaysia, Visiting Professor at the Universiti Kebangsaan Malaysia (UKM), Visiting Professor at the Al-Farabi Kazakh National University, Kazakhstan.

PROF. DR. VIQAR UDDIN AHMAD Hilal-i-Imtiaz, Sitara-i-Imtiaz, Distinguished National Professor (HEC), Lifetime Achievement Award (HEC), Ph.D. (Organic Chemistry), University of Karachi (1966), Dr. rer.nat. (Synthetic Chemistry) Bonn University, Germany (1968), present Full Professor, H.E.J. Research Institute of Chemistry, University of Karachi (1976), Alexander von Humboldt Fellow, Erlangen, Germany (1988-1989), Doctor of Science (D.Sc.) University of Karachi (1992), Senior Fulbright Fellow, Ithaca, New York, USA (1993),Dean, Faculty of Science, University of Karachi (1994-2000), Research publications – 454, books – 09, patents – 05, Visited USA, UK, France, Brazil, Mexico, South Africa, Italy, Egypt, Malaysia, Thailand, South Korea, Sri Lanka, India and Saudi Arabia. 13

PROF. DR. BINA S. SIDDIQUI Sitara-e-Imtiaz, Tamgha-e-Imtiaz, Senior Professor, ICCBS, Khwarizmi Laureate, Distinguished National Professor of HEC, D.Sc. (University of Karachi, Pakistan Life Time Academic Achievement Award, HEC, Pakistan, First Dr. Abdus Salam Prize in Chemistry, Fellow, The Third World Academy of Sciences for the Developing World (TWAS), Fellow, Third World Organization for Women inScience (TWOWS), Fellow, Pakistan Academy of Science (PAS), Fellow, Chemical Society of Pakistan (CSP), 340 publications including 245 research publications, 18 patents and 77 chapters in books PROF. DR. AHSANA DAR FAROOQ Professor (Pharmacology), International Research Coordinator, Ph.D. (Pharmacology), University of Cambridge, U.K. (1992), Research publications (50), Books (19), patents (3), Visited National Cancer Institute (NCI), Frederick Maryland, U.S.A. (1994), Visiting Professor, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences, Peking Union Medical College, BeijingChina (2005), Member Academic Council, University of Karachi, Member BASR Ziauddin University, Karachi.

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DR. FARZANA SHAHEEN UNESCO L’OREAL Fellow (2004), Fulbright Fellow (2008), Dr. M. Raziuddin Siddiqi prize (2006), OWSD Young Women Scientist Award (2011), Ph.D. (H. E. J. Research Institute of Chemistry, 1995-2000), Research O{cer (H.E.J. Research Institute of Chemistry, 2000-2001), Assistant Professor (H.E.J. Research Institute of Chemistry, 20012011), Area of research: Natural Product chemistry and combinatorial synthesis of cyclic peptides and peptidomimetics, Research publications- 50, patents -2, Visited University of Southampton under UNESCO L’OREAL Fellowship Program, 2005, Fulbright Fellow and Visiting Assistant Professor at UC-Davis during 2008-2009. DR. SHABANA USMAIN SIMJEE Assistant Professor, Pharmacology, H. E. J. Research Institute of Chemistry, British Council Visitor, Under Higher Education Link Programme Scheme between HEC (Pakistan) and British Council (2009), Visiting Professor, Transfusion Medicine Unit, St. Michael’s Hospital, Toronto, Canada (2004-2005), Visiting Scholar, Programme in Integrative Biology, The Hospital for Sick Children Research Institute, Toronto, Canada (2005),Visiting Faculty, FAST Institute of Computer Science, National University of Emerging Sciences, Karachi, Pakistan (2003), Assistant Professor, Department of Biochemistry, Baqai Medical University, Karachi, Pakistan (2002-2003), Research Publications (18), Patent (1), Reviewer; International Immunopharmacology, Pharmaceutical Biology, Pakistan Journal of Pharmaceutical Sciences, Journal of Basic and Applied Sciences (Pakistan). 15

SCIENTIFIC VISITS (KAZAKHSTAN) PROF. DR. SC. ABILOV ZHARILKASYN Member of Academia of Science High School RK Honoured Worker Education of RK Laureate Prize “Best Scientic Scientist RK” x 1966-1971 – High Education of Chemistry Kirov Kazakh State University. x 1971-1982 – Research fellow Kirov Kazakh State University x 1982- Ph.D. (Colloidial chemistry) Kazakh National University. x 1982-1994 – Associated Professor KazNU. x 1993 – Doctor of Science (D.Sc.) (chemistry of high-molecular compounds) KazNU. x 1996 – present Full Professor KazNU. x 1996-2000 – Head of chair of organic chemistry and chemistry of natural products. x 2000-2009 Dean of chemistry department KazNU. x 2009/present – Head of chair of chemical technology of organic compounds, natural substances and polymers. x Research publications – 400, books – 17, patents – 50 RK, temporary pharmacopeia articles – 14 of RK. x Inventor of original preparations “Alhidin”, “Gauhar”, “Zhantak”, “Biosed-K”, “Sanzhar”, “Limonidine” x Visited in the year 1998 as a member of National Academy of Sciences, RK

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PROF. DR. SC. BURASHEVA GAUHAR SHAKHMANOVNA Laureate Prize “Best Scientic Scientist RK” x 1967-1972- high education of chemistry Kirov Kazakh State University x 1973-1981 Research fellow Kazakh National University x 1981 – Ph.D. (Chemistry of natural products) KazNU x 1994- Associate Professor KazNU x 2004 – Doctor of Science (D.Sc.) (Bioorganic Chemistry) KazNU x 2008 /present Full Professor KazNU x Research publications – 170, books – 2, patents – 21 RK, pharmacopeia article – 1, temporary pharmacopeia articles – 4 of RK. Inventor of original preparations “Alhidin”, “Gauhar”, “Zhantak”. x Visited Karachi in the year 2000. PROF. DR.SC. MUZICHKINA RAISA ALEKSEEVNA x 1958-1962- high education of chemistry Kirov Kazakh State University x 1962 -1967 Undergraduate student Kirov Kazakh State University x 1968-1969 – Assistant Professor Kirov Kazakh State University x 1970-1977 – Lecturer Kirov Kazakh State University x 1978-1991 – Associate Professor Kirov Kazakh State University 17

x 1990 – Doctor of Science (D.Sc.) (Bioorganic Chemistry, Chemistry of Natural and Physiology-Active Compounds) x 1992 – present – Full Professor Al-Farabi Kazakh National University x Research publications – 347, books – 8, patents – 38 of Russia and RK, Pharmacopeia articles – 18 of RK. x Inventor of original antidermatic preparation “RAMON” x Visited in the year 1998 as a member of National Akademy of Sciences RK (Islamabad, Faisalabad) DR. TURMUKHANOVA MIRGUL ZHURAGATOVNA x Associate Professor x 1970-1975 – high education of chemistry Kirov Kazakh State University x 1976-1978 Research fellow KazNU x 1978-1981 Post-graduate student KazNU x 1998 – Ph.D. (Organic Chemistry) KazNU x 1995/present – Associate Professor KazNU x 2010 – Doctor of Science (D.Sc.) x Research publications – 160, books – 4, patents – 5 Republic of Kazakhstan and 4 Russia x Visited Karachi in the year 2007.

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DR. BATES KUDAIBERGENOVA MALIKOVNA x 1998-2002: B.Sc. Department of Chemistry, Al-Farabi Kazakh National University x 2002-2004: M.Sc. Department of Chemistry, Al-Farabi Kazakh National University x 2004-2005: Specialist of Laboratory of Physicochemical Methods Analyses (AlFarabi Kazakh National University) x Nov 2006 – Dec 2006: Research Trainee, H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Pakistan. Supervisor- Prof., Dr. M. Iqbal Choudhary. x Oct 2007 – Nov 2007: Research Trainee, Institute of Chemistry Tashkent (Uzbekistan) x Nov 2007 – March 2008: Research Trainee, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Pakistan. Supervisor- Prof., Dr. M. Iqbal Choudhary. x 2008-Ph.D. (organometalic chemistry, catalises and natural product chemistry) x July 2008 (15 days); Research fellow, Novosibirsk University, Novosibirsk, Russia. x 2008/present – Senior-lecturer. Department of Chemistry, Al-Farabi Kazakh National University x Research publications 38, innovation patents of Republic of Kazakhstan-3. x Postdoctoral Research fellow: in 2012 y. HEJ Research Institute of chemistry University of Karachi. International Center of Sciences, Karachi, Pakistan.

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TRAINING OF YOUNG SCHOLARS DR. MIFTAKHOVA ALFIRA Ph.D. x 1992-1996 – B.Sc. (chemistry) Al-Farabi Kazakh National University x 1996-1998 - M.Sc KazNU x 1998-2000 - post-graduate student KazNU x 2002- Ph. D. (bioorganic chemistry) x Research publications 15, patents of Republic of Kazakhstan-1 x Research Fellow HEJ Research Institute of chemistry University of Karachi. International Center of Sciences, Pakistan. Supervisor- Prof. Dr. Viqar Uddin Ahmad (2000-2001). DR. SULTANOVA NURGUL ADAIBAEVNA x 1993-1998- B.Sc. (chemistry) Al-Farabi Kazakh National University x 1998-2000 - M.Sc KazNU x 2000-2002 - post-graduate student KazNU x 2004- Ph. D. (bioorganic chemistry) x 2004 -2006 – Senior-lecturer KazNU x 2008 /present Associated Professor KazNU x 2010- Doctor of Science (D.Sc.) x

Research publications 40, patents 5 of Republic of Kazakhstan, text book-1

x Research fellow H. E. J. Research Institute of chemistry University of Karachi. International Center of Sciences, Pakistan. Supervisor- Prof., Dr. M. Iqbal Choudhary (2000-2001). 20

DR. KORULKINA LIRA MAZHITOVNA Ph.D. x 1986-1990- high education of chemistry Kirov Kazakh State University x 2001-2003 research fellow KazNU x 2003-2005- post-graduate student KazNU x 2006- Ph. D. (bioorganic chemistry) x Research publications 15, previously patents 5 of Republic of Kazakhstan x Research fellow H. E. J. Research Institute of chemistry University of Karachi. International Center of Sciences, Pakistan. Supervisor- Prof., Dr. M. Iqbal Choudhary (2003). DR. UMBETOVA ALMAGUL KENDEBAEVNA Ph.D. x 1996-2000 - B.Sc. (Chemistry) Al-Farabi Kazakh National University x 2000-2002- M.Sc. KazNU x 2007- Ph. D. (Bioorganic chemistry) x 2007/ present - Teacher, KazNU x Research publications 20, 3 patents of Republic of Kazakhstan x Research fellow HEJ Research Institute of chemistry University of Karachi. International Center of Sciences, Pakistan. Supervisor - Prof. Dr. M. Iqbal Choudhary (2004-2005).

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DR. YESKALIYEVA BALAKYZ KYMYZGALIYEVNA Ph.D. x 1995-1999- B.Sc. (Chemistry) Al-Farabi Kazakh National University x 1999-2001- M.Sc. Al-Farabi KazNU x 2007- Ph. D. (Bioorganic chemistry) x 2005/present- Senior-lecturer KazNU x Research publications 25 and 3 patents of Republic of Kazakhstan. x Research fellow HEJ Research Institute of chemistry University of Karachi. International Center of Sciences, Pakistan. Supervisor- Prof. Dr. Viqar Uddin Ahmed and Prof. Dr. M. Iqbal Choudhary (20032005).

DR. KARZHAUBEKOVA ZHANNAT ZHUMABEKOVNA Ph.D. x 1997-2001 - B.Sc. (Chemistry) Al-Farabi Kazakh National University x 2001-2003 - M.Sc. KazNU x 2007- Ph. D. (bioorganic chemistry) x Research publications 15, innovation patents – 2 of Republic of Kazakhstan. x Research fellow H. E. J. Research Institute of chemistry University of Karachi. International Center of Sciences, Pakistan. Supervisor- Prof. Dr. Bina Siddiqui S, (2004-2005).

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MS. MYNBAEVA ZHANAR M.Sc.Post-graduate Student x2000-2004- B.Sc. (Chemistry) Eurasian national university named after L.N. Gumilev, Astana x2004/ present - Post-graduate student – Eurasian National University named after L.N. Gumilev, Astana xResearch publications 21 patents of Republic of Kazakhstan-3 xResearch fellow H. E. J. Research Institute of Chemistry, University of Karachi. International Center of Sciences, Pakistan. Supervisor- Prof. Dr. M. Iqbal Choudhary (2007).

MS. BUTABAEVA KALAMKAS ZHANARBEKOVNA M.Sc. Post-graduate Student x 2000-2005- high education of Chemistry Al-Farabi Kazakh National University x

2005/presentKazNU

post-graduate

student

x Research publications 5 x Research Fellow H. E. J. Research Institute of chemistry University of Karachi. International Center of Sciences, Pakistan. Supervisor- Prof. Dr. Bina S. Siddiqui (2007, 2009)

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RESEARCH PROJECTS PAK-KAZAKH SCIENTIFIC COLLABORATION PROJECT ENTITLED, “STUDIES on the BIOLOGICALLY ACTIVE METABOLITES from the PLANTS of CENTRAL ASIA”

Chemical investigation of genus Tamarix – T. hispida, T. ramosissima N. A. Sultanova, M. Iqbal Choudhary, T. Makhmoor, V. B. Omurkamzinova, Atta-ur-Rahman, and Z. A. Abilov The object of investigation – Aerial part of two species of genus Tamarix – T. hispida, T. ramosissima belongs to the Tamaricaceae family growing in the various regions of Kazakhstan.

Isolation of Biologically Active Compounds from T. ramosissima and T. hispida. The air-dried and crushed plant material was macerated at the room temperature in 50%- acetone-water thricely for 24 hours. The combined acetone-water extracts were concentrated to dryness (50 gm). The concentrated acetone-water extract was dissolved in distilled water and extracted successfully with benzene followed by chloroform and ethyl acetate. Quantitative contamination of extracts and water solutions was analyzed by GLC, PC and TLC methods. Benzene and chloroform extracts of Tamarix contain chlorophylls, lipophilic substances, high saturated and unsaturated carboxylic acids and terpenoids; ethyl acetate extracts-terpenoids, phenolic acids, glycoside forms of flavonoids and tannins; water solutions-aminoacids, carbohydrates, sulphate forms of flavonoids and hydrolyzable tanning. Isolation of individual compounds was carried out by means of adsorption distributing chromatography (polyamide, silica gel), gel 24

chromatography (LH-20), preparative HPLC, PC and TLC. According to the scheme of BAS 4 terpenoids (1, 2, 4, 20), 1 long chain alcohols (3), 6 phenolic acids (compounds 5-7, 12, 13), 11 flavonoids (16-19, 21-25, 27, 32), 2 cinnamoyl (26, 33) and 2 hydrolizable tannins (28, 31) were isolated. Four phenolic acids were identified by HPLC method (8-11). Investigation of Terpenoids According to the results of TLC (sulfate of cerium) and positive reaction with the Liberman-Burhard reagent. It was found that stated that the main components of benzene and chloroform extracts are terpenoids. On the basis of physical-chemical analytical data and in comparison with the literature data compound 1 is β-carotene; 2phytol; 3- β sitosterol. Compounds 1 and 2 are new for the genus Tamarix. Earlier β-sitosterol was identified by other scientists for Tamaricaceae families. The complete physical-chemical characteristics of terpenoids from T. hispida и T. ramosissima are presented in Table-1. Compound 20 was related to pentacycle tri-terpenoids because of claret coloring by sulfate of cerium and Liberman-Burhard reaction. The UV spectrum showed absorptions at 216, 244, 255, 305 and 372 nm. The IR spectrum showed absorptions ester (1691 cm-1), aromatic (1600-1460 cm-1), methyl, methyne, methylene (2864-2933 cm-1) and hydroxyls groups (3411 cm-1). For the confirmation of ester groups, we provided alkaline hydrolyses (3% KOH in MeOH). Work up in the usual way afforded a product which was chromatographed over silica-gel column using chloroform as eluent to afford compound 20 a with m.p. 270-272 oС and in the hydrolizate identified coffeic acid by TLC and PC. The HR EI/MS of 20 and 20 a had showed the highest peak at m/z 438.3507 corresponding to the formula C30H46O2. The negative FAB MS of 20 showed the pseudo molecular ion at m/z 617.432 corresponding to the molecular formula C39H53O6; for 20a over EI MS molecular ion at m/z 456 corresponding to the molecular formula C30H48O3. The mass difference between HREI MS and FAB MS was due to the loss of 3,4dihydroxy cinnamoyl group (C9H7O4), which was further confirmed by the 1H- and 13C-NMR spectroscopy. The characteristic fragments at m/z 248, 203, 189 and 133, resulted from the retro-Diels Alder cleavage, suggested a taraxer-14-ene skeleton with a carboxylic group. NMR spectroscopy of 20 and 20 a provides information about a triterpene moiety and the substituted aromatic ring including a transoriented double bond. Seven 3H singlets at  0.87, 0.92, 0.93, 0.94, 0.96, 0.97 and 0.98 represented the seven tertiary methyls. The olefinic proton 25

appeared as a double doublet at  5.57 (1H, dd, J = 8.0 Hz, J = 3.5 Hz, H15). The chemical shift, multiplicity and coupling constants of the olefinic proton and also the chemical shifts of the tertiary methyls were in accordance with those of taraxer-14-ene skeleton. The H-3 proton 20 resonated at  4.69 from the coupling constant (J = 2.5 Hz) and for 20 a as broad singlet at  4.41 (W1/2 =2.5 Hz) which indicated that H-3 was equatorially oriented. The three aromatic protons appeared at  7.03 (1H, d, J = 2.0 Hz, H-2"), 6.76 (1H, d, J = 8.0 Hz, H-5") and 6.92 (1H, dd, J = 8.0 Hz, J= 2.0 Hz, H-6"). The coupling constant relationship between these protons established a 1,3,4-trisubstituted aromatic ring. Two 1H doublets at  6.26 and 7.51 (J = 16.0 Hz) represented the transsubstituted olefinic H-2' and H-3'. This information indicated the presence of an O-3, 4-Dihydroxy cinnamoyl group in 20. The α- position of the O-3,4-Dihydroxy cinnamoyl group at C-3 was confirmed by the small 3JH,H coupling (2.5 Hz) of the equatorial H-3. The complete 1HNMR assignments are presented in Table 1. The 13C-NMR of 20 showed seven methyls, ten methylenes, ten methines and twelve quaternary carbon signals. The signals for eight olefinic carbons (C-2', C-3', C-1", C-2'', C-3", C-4", C-5", C-6"), one ester carbonyl (C-1'), a carboxyl carbon (C-28) and one double bond carbons (C14 and C-15) resonated at  115.5, 146.5, 127.4, 115.0, 146.4, 149.2, 117.7, 122.7, 168.0, 182.2, 161.3 and 116.2, respectively. The position of COOHmoiety at C-17 was confirmed by a quaternary carbon signal at  52.10 which was assigned to C-17. The complete 1H- and 13C-NMR chemical shifts and multiplicities of each protonated carbon are listed in Table 2. The HMBC (heteronuclear multiple bond connectivity) spectrum of 20 showed long-range heteronuclear connectivity which was used to place various functionalities on the taraxer-14-ene skeleton. The H-18 exhibited interaction with C-28 ( 182.2) further confirming the location of COOH at C-17. The proton at  4.69 showed a long-range correlation with the C-1' ( 168.0), indicating that the 3, 4-Dihydroxy cinnamoyl group was located at C-3. On the basis of the above mentioned spectral observations, compound 20 was deduced to be 3--3",4"-Dihydroxy trans-cinnamoyl-oxy-D-friedoolean-14-en-28-oic acid, 20a – 3--oxy-dfriedoolean-14-en-28-oic acid – epialeuritolic acid. Early was 3 Acetyl-taraxer-14-en-28-oic acid was isolated from Phytolacca acinosa which is structurally related to 20 except that acetyl group at C-3 is in 26

position. The compounds 20 and 20a are new and not mentioned in literature earlier. 29

30

O

20 19

27

21 22

18 11

25

26

H

1'

R=

17

13 14

9

3'

20

12

10

3

5 4

RO

8

H 6

H 23

2'' 1''

OH 3''

COOH

16

28

6''

1 2

2'

4'' 5''

15

OH

7

20a

R= H

24

Table 1 Physical-chemical characteristics of terpenoids from T.hispida and T. ramosissima Compounds - carotene (1) С40Н56, red rhombic crystals m.p. 184-186oС (from hexane), Rf 0.50 (Hex-Chl 9:1).

Phytol (2), С20Н40О, white oil, Д23 +0.13 (С. 0.4; СНCI3), Rf 0.40 (Hex-Chl 9:1).

-sitosterol (4), С29Н50О- white crystals m.p. 134-136oС, Д23 +11 (С. 0.2; СНCI3),

Spectroscopic characteristics Mass-spectrum, m/z (%): 536 (66) М, 444 (6), 268 (11), 183 (6), 145 (25), 105 (51), 69 (100). 1Н NMR (500 МHz, СDСI3, , ppm., J/Hz): 1.47 (m, Н-2, Н-2), 1.62 (m, Н-3, Н-3), 2.02 (m, Н-4, Н-4), 7.39 (d, J=11.0, Н-6, Н-6), 6.19 (d, J=16.0, Н-7), 6.51 (dd J1=15.0, J2=11.0Hz, Н-7), 6.13 (d, J=16.0, Н-8), 6.66 (d, J=15.0, Н-8), 6.16 (d, J=11.0, Н-10), 6.37 (d, J=11.0, Н-10), 6.67 (dd, J1=11.0, J2=15.0, Н-11), 6.63 (dd, J1=11.0, J2=15.0 Н-11), 6.36 (d, J=15.0, Н-12), 6.47 (d, J=15.0, Н-12), 6.29 (d, J=11.0, Н-14), 6.32 (d, J=11.0, Н-14), 6.67 (m, Н-15), 6.65 (m, Н-15), 1.03 (s, Н-16, Н-16), 1.02 (s, Н-17, Н-17), 1.7 (s, Н-18, Н-18), 1.98 (s, Н-19), 2.0 (s, Н-19), 1.99 (s, Н-20), 1.98 (s, Н-20). Mass-spectrum, m/z (%): 296 (14) М, 296 (15), 280 (4), 278 (11), 216 (3), 196 (14), 167 (4), 139 (8), 126 (30), 123 (71), 112 (11), 109 (18), 67 (26), 57 (36). 1Н NMR (500 МHz, СDСI3, , ppm., J/Hz): 5.40 (1Н, t, J=6.9), 4.13 (2 Н, d, J=6.9), 1.96 (2Н, t, J=7.6), 1.63 (3Н, s), 1.54-1.00 (19Н, m), 0.87 (9Н, d, J=6.6), 0,84 (3Н, d, J=6.5). Mass-spectrum, m/z (%): 414 (100), 399 (28), 329 (35), 275 (5), 273 (17), 164 (3), 83 (12). 1Н NMR (500 МHz, СDСI3, , ppm., J/Hz): 0.66 (3 Н, s, Н-18), 5.30 (1Н, br.s. Н-6), 0.83 (3Н, t, Н-29), 0.88 (3Н, d, J =6.5, Н-21), 0.82 (3Н, d, J=6.2, Н-26), 0.84 (1Н, d), 0.78 (3Н, d, J=6.2, Н-27).

27

Isotamarixen (20), С39Н54О6- white powder m.p. 196-1980C, Д22 – 22 (С. 0.04; СН3ОН), Rf 0.35 (Dichl-Met 9.7:0.3).

Epialeuritolic acid (20а), С30Н48О3- white powder m.p. 270-2720C, Д22 –13.50 (С. 0.04; СНCI3), Rf 0.20 (DichlMet 9.7:0.3).

UV-spectrum, max (СН3ОН), nm: 216, 244, 255, 305, 372. IR (KBr, , cm –1): 3411, 1259, 1691, 1600, 812. Massspectrum FABMS (-ve), m/z (%): 617 М-1 (20), 437 (15), 247 (8), 206 (5), 188 (90), 132 (5). 1Н NMR (500 МHz, CD3OD-CDCI3, , ppm, J/Hz): 1.30 (2Н, m, Н-1), 1.95 (2Н, m, Н-2), 4.69 (1Н,t, J=2.5, Н-3), 1.35 (1Н, m, Н-5), 1.40 и 1.60 (2Н, m, Н-6), 1.40 – 1.95 (2Н, m, Н-7), 1.55 (1Н, m, Н-9), 1.55 – 1.65 (2Н, m, Н-11), 1.60 and 1.76 (2Н, m, Н12), 5.57 (1Н, dd, J1=3.5, J2 =8.0, Н-15), 1.96 – 2.37 (2Н, m, Н-16), 2.37 (1Н, m, Н-18), 1.10 – 1.24 (2Н, m, Н-19), 1.05 и 1.6 (2Н, m, Н-21), 1.5 и 1.7 (2Н, m, Н-22), 0.87 (3Н, s, Н23), 0.92 (3Н, s, Н-24), 0.97 (3Н,s, Н-25), 0.98 (3Н, s, Н-26), 0.94 (3Н, s, Н-27), 0.96 (3Н, s, Н-29), 0.93 (3Н, s, Н-30), 6.26 (1Н, d, J=16.0, Н-2), 7.51 (1Н, d, J=16.0Hz, Н-3), 7.03 (1Н, d, J=2.0Hz, Н-2), 6.76 (1Н, d, J=8.0, Н-5), 6.92 (1Н, dd, J1=2.0, J2=8.0, Н-6). IR (KBr, , cm –1): 3448, 1690, 1460, 1386, 1061, 993. Mass-spectrum, m/z (%): 456 (5), 438 (3), 248 (49), 207 (30), 189 (100), 133 (26); FD: 438  М-Н2О +. 1Н NMR (500 МHz, CD3OD-CDCI3, , ppm., J/Hz): 1.28 (2Н, m, Н-1), 1.92 (2Н, m, Н-2), 4.41 (1Н,br.s, W1/2=2.6 Hz, Н-3), 1.34 (1Н, m, Н-5), 1.40 и 1.60 (2Н, m, Н-6), 1.40 – 1.90 (2Н, m, Н-7), 1.53 (1Н, m, Н-9), 1.53 – 1.64 (2Н, m, Н11), 1.60 и 1.73 (2Н,m, Н-12), 5.53 (1Н, dd, J1=3.5, J2 =8.0, Н-15), 1.90 и 2.35 (2Н, m, Н-16), 2.35 (1Н, m, Н18), 1.10 и 1.22 (2Н, m, Н-19), 1.02 и 1.55 (2Н, m, Н-21), 1.5 и 1.7 (2Н, m, Н-22), 0.85 (3Н, s, Н-23), 0.90 (3Н, s, Н-24), 0.95 (3Н, s, Н-25), 0.97 (3Н, s, Н-26), 0.93 (3Н, s, Н-27), 0.95 (3Н, s, Н-29), 0.92 (3Н, s, Н-30).

Investigation of Flavonoids The flavonoids were isolated from the ethylacetate extract (compounds 16-19, 21-25, 27) and water solution (32). On the basis of positive reactions with ammonia vapors, UV-light, anthocyanidinic sample and chromatographic behavior (PC) with the following chromatography on the silica gel, polyamide and preparative PC and TLC were isolated and determinate 11 flavonoids. On the basis of physical and chemical characteristics, spectral analysis methods and according to the literature data, compound 16 was identified as – 3-0-L-rhamnosid-7,4-trihydroxyflavon (аfzelin); 17 – 3-O-β-D-gluco-pyranoside -5,7,3′,4'-tetrahydroxyflavon (isoquercetrine), 18 – 3-O-α-L28

rhamnopyranoside-5,7,3′,4'-tetrahydroxyflavon (quercetrine); 19-3-O-βD-glucopyranoside -5,4′ Dihydroxy-7,3'-methoxyflavon (flavouazorine); 21- 3,5-Dihydroxy-4', 7-dimethoxyflavon; 22- 3,5,4- trihydroxy- 7-methoxyflavon (rhamnocetrin); 23 – 3, 5, 7, 4 '-tetrahydroxyflavon; 24 – 3, 5, 7,4'-tetrahydroxy-3'-methoxyflavon (isorahmnetin); 25 – 3,5,7,3'tetrahydroxy-4'-methoxyflavon (tamarixetine); 27 – 3,5,7,3′,4'-pentahydroxyflavon (quercetine); 32-potassium salt 3-O-sulphate of tamarixetine (tamarixin). The compounds 16 and 19 are new for genus Tamarix. The physical-chemical characteristics of flavonoids from T.hispida и T.ramosissima are presented in Table 2. R2 R3

O

R1

OR OH

3-0--L-rhamnosid7,4-trihydroxyflavon (аfzelin) (16)

O

R1= R3=OCH3; R2=H R= O H3C

O

HO HO

-3-O-β-D-glucopyranoside -5,4′ Dihydroxy-7,3'- methoxyflavon (flavouazorine) (19)

HO

R1=OH; R2= R3=OCH3 R= O HOH2C

O

HO HO

HO

29

Table 2 Physicochemical characteristics of flavonoids from T. hispida and T. ramosissima Compounds 3,5-Dihydroxy4',7-dimethoxyflavon (21), m.p. 180-182 oС (МеОН); Rf 0.91 (BAW 1:4:5), 0.45 (Chl.-Met 8:2).

3,5,4Trihydroxy-7methoxy-flavon (22), m.p. 223-225 oС

Spectroscopic characteristics Mass-spectrum, m/z, %: 300 (82), 285 (11), 257 (9), 229 (8), 167 (10), 152 (5), 135 (27), 83 (47), 121(10), 55 (100). 1Н NMR (500 МHz, С5D5N, , ppm., J/Hz): 8.52 (2Н, d, J=9.0, Н-2, Н-6); 7.16 (2Н, d, J=9.0, Н-3, Н-5); 6.70 (1Н, d, J=2.0, Н-8); 6.58 (1Н, d, J=2.0, Н-6); 3.76, 3.74 (6Н, s, ОСН3). UVspectrum, max (СН3ОН), nm: 267, 364; СН3COОNa 267, 364; СН3COОNa+H3BO3 268, 363; СН3ОNa (), AICI3 270, 423; AICI3/HCI 270, 423. Mass-spectrum, m/z, %: 314 (100), 299 (8), 285 (4), 271 (10), 213 (5), 167 (12), 152 (6), 135 (27), 55.1 (100), 121 (8), 83 (47), 55 (90). 1Н NMR (500 МHz, С5D5N, , ppm., J/Hz): 8.05 (2Н, d, J=10.0, Н-2, Н-6); 6.92 (2Н, d, J=10.0, Н-3, Н5); 6.31 (1Н, d, J=2.0, Н-8); 6.15 (1Н, d, J=2.0, Н-6);

(МеОН); Rf 0.90 (BAW), 0.43 (ChlMet 8:2).

3.76 (3Н, s, ОСН3). UV-spectrum, max (СН3ОН), nm: 270, 364; СН3COОNa 268, 365; СН3COОNa+H3BO3 260, 360; СН3ОNa 266, 410 (), AICI3 350, 420; AICI3/HCI 350, 420.

3, 5, 7, 4 'Tetrahydroxyflavon (23), m.p. 278-280 oС (МеОН); Rf 0.80 (BAW), 0.40 (ChlMet 8:2).

Mass-spectrum, m/z, %: 286 (67), 257 (4), 229 (1), 152 (10), 134 (20), 121 (13), 52 (90). 1Н NMR (500 МHz СD3ОD, , ppm., J/Hz): 8.10 (2Н, d, J=8.8, Н-2, Н-6); 6.93 (2Н, d, J=8.8, Н-3, Н-5); 6.40 (1Н, d, J=2.0, Н-8); 6.18 (1Н, d, J=2.0, Н-6). UV-spectrum, max (СН3ОН), nm: 260, 367; СН3COОNa 262, 371; СН3COОNa+H3BO3 260, 367; СН3ОNa 256, 326, AICI3 263, 430; AICI3/HCI 262, 427.

3, 5, 7, 4'Tetrahydroxy-3'methoxyflavon (24), m.p. 304-306 oС (МеОН); Rf 0.85 (BAW), 0.40 (ChlMet 8:2).

Mass-spectrum, m/z, %: 316 (15), 301 (100), 286 (21), 273 (81), 229 (4), 167 (3), 152 (6), 137 (15), 118 (7), 82 (27), 57 (78). 1Н NMR (500 МHz, С5D5N, , ppm., J/Hz): 8.53 (1Н, d, J=2.0, Н-2); 8.13 (1Н, dd, J1=2.0, J2=8.0, Н-6); 7.12 (1Н, d, J=8.0, Н-5); 6.78 (1Н, d, J=2.0, Н-8); 6.73 (1Н, d, J=2.0, Н-6); 3.90 (3Н, s, ОСН3). NMR 13С: 157.54 С-2; 138.38 С-3; 177.44 С-4; 162.46 С-5; 99.27 С-6; 165.64 С-7; 94.35 С-8; 157.54 С-9; 104.51 С-10; 125.60 С-1; 112.12 С-2; 148.06 С-3; 147.13 С4; 116.41 С-5; 120.44 С-6; 55.89 (ОСН3). UV-spectrum, max (СН3ОН), nm: 255, 369; СН3COОNa 270, 380; СН3COОNa+H3BO3 256, 370; СН3ОNa 275, 423, AICI3 265, 428; AICI3/HCI 264, 428.

30

3,5,7,3'Tetrahydroxy-4'methoxyflavon (25), m.p. 240-242 oС (МеОН); Rf 0.83 (BAW), 0.35 (ChlMet 8:2)

Mass-spectrum, m/z, %: 316 (100), 301 (90), 287 (35), 273 (20), 189 (5), 167 (5), 156 (10), 137 (30), 128 (80), 118 (5), 108 (25), 57 (98). 1Н NMR (300 МHz, СD3OD, , ppm., J/Hz): 6.10 (1Н, d, J=2.0, Н-8); 6.00 (1Н, d, J=2.0, Н-6), 7.60 (1Н, d, J=2.3, Н-2); 7.70 (1Н, dd, J1=2.0, J2=8.0, Н-6); 7.03 1Н, d, J=8.7 Н-5; 3.90 (3Н, s, ОСН3). NMR13С: 158.42 С-2; 134.30 С-3; 178.71 С-4; 158.78 С-5; 96.05 С-6; 163.02 С-7; 96.06 С-8; 158.42 С-9; 101.78 С-10; 123.02 С-1; 112.14 С-2; 147.24 С-3; 151.59 С-4; 116.60 С-5; 124.61 С-6; 55.34 (ОСН3). UVspectrum, max (СН3ОН), nm: 267, 368; СН3COОNa 275, 380; СН3COОNa+H3BO3 268, 370; СН3ОNa 310, 380 (), AICI3 295, 390; AICI3/HCI 295, 390.

3,5,7,3′,4'Pentahydroxyflavon (27), m.p. 310-312 oС (МеОН); Rf 0.70 (BAW), 0.30 (ChlMet 8:2).

Mass-spectrum, m/z, %: 302 (100), 273 (7), 245 (7), 229 (5), 153 (8), 137 (9), 127(10), 83 (5), 68 (17). 1Н-NMR (500 МHz, С5D5N, , ppm., J/Hz): 6.76 (1Н, d, J=2.5, Н-8); 6.72 (1Н,d, J=2.5, Н-6), 8.63 (1Н, d, J=2.0, Н-2); 8.12 (1Н, dd, J1=2.5, J2=8.5, Н-6), 7.39 1Н, d, J=8.5, Н-5). UV-spectrum, max (СН3ОН), nm: 255, 372; СН3COОNa 280, 390; СН3COОNa+H3BO3 272, 390; СН3ОNa 246, 330; AICI3 266, 428; AICI3/HCI 265, 427.

3-O--Lrhamnosid-7,4trihydroxyflavon (16), m.p.168-170 oС (Н2О-МеОН); Д20 -106 (С. 0.1; Н2ОМеОН); Rf 0.70 (BAW), 0.35 (6% НОАс)

Маss-spectrum, m/z, %: 431 (10), 285 (10), 275 (15), 256 (7), 184 (100), 152 (20), 118 (10), 51 (10). 1Н NMR (500 МHz, С5D5N, , ppm., J/Hz): 7.79 (2Н, d, J=8.8, Н-2, Н-6); 6.95 (2Н, d, J=8.8, Н-3, Н-5); 6.38 (1Н, d, J=2.0, Н-8); 6.21 (1Н, d, J=2.0, Н-6); 5.37 (1Н, d, J=2.0, Н-1); 0.92 (3Н, d, J=6.0, СН3). NMR 13С: 158.0 С-2; 135.98 С-3; 179.12 С-4; 163.07 С5; 99.87 С-6; 165.95 С-7; 94.67 С-8; 157.80 С-9; 105.58 С-10; 121.93 С-1; 131.54 С-2; 116.46 С-3; 161.73 С-4; 131.54 С-5; 116.46 С-6; 103.89 С-1; 72.04 С-2; 73.36 С-3; 72.62 С-4; 72.07 С-5; 18.36 С-6. UV-spectrum, max (СН3ОН), nm: 265, 340; СН3COОNa 265, 344; СН3COОNa+H3BO3 265, 340; СН3ОNa 272, 390; AICI3 273, 389; AICI3/HCI 274, 389.

3-O-β-D-Glucopyranoside -5,7,3′,4'tetrahydroxyflavon (17), m.p.235-237 oС (Н2О-МеОН); Д20 -70.1 (С. 0.14; Н2ОМеОН); Rf 0.60 (BAW), 0.20 (6% НОАс)

Маss-spectrum, m/z, %: 465 (10), 303 (8), 277 (11), 259 (6), 185 (100), 152 (30), 136 (15), 52 (10). 1Н NMR (500 МHz, С5D5N, , ppm., J/Hz): 5.62 (1Н, d, J=8.0, Н-1); 6.66 (1Н, d, J=2.0, Н-8); 6.46 (1Н, d, J=2.0, Н-6); 7.70 (1Н, d, J=2.0, Н-2); 7.30 (1Н, d, J=8.0, Н-5); 7.60 (1Н, d, J=8.0, Н-6). UVspectrum, max (СН3ОН), nm: 258, 360; СН3COОNa 272, 380; СН3COОNa+H3BO3 265, 378; СН3ОNa 262, 434; AICI3 273, 400; AICI3/HCI 260, 400.

31

3-O-ά-LRhamnopyranoside5,7,3′,4'-tetrahydroxyflavon (18), m.p.186-188 oС (Н2ОМеОН); Д20 -83.0 (С. 0.12; Н2ОМеОН); Rf 0.70 (BAW), 0.25 (6% НОАс)

Маss-spectrum, m/z, %: 449 (7), 303 (10), 277 (30), 259 (9), 207 (40), 185 (100), 167 (20), 152 (15), 137 (10), 50 (8). 1Н NMR (500 МHz, С5D5N, , ppm., J/Hz): 8.00 (1Н, d, J=2.0, Н-2); 7.27 (1Н, d, J=8.0, Н-5); 6.67 (1Н, d, J=2.0, Н-8); 6.26 (1Н, d, J=2.0, Н-6); 7.69 (1Н, dd, J1=8.5, J2=2.0 Н-6); 5.06 (1Н,d, J=2.0, Н-1); 1.47 (3Н, d, J=7.8 СН3). UV-spectrum, max (СН3ОН), nm: 256, 355; СН3COОNa 268, 365; СН3COОNa+H3BO3 262, 367; СН3ОNa 262, 390, AICI3 265, 400; AICI3/HCI 266, 390.

3-O-β-D-Glucopyranoside -5,4′-Dihydroxy-7,3'- methoxyflavon (19), m.p. 160-162 oС (МеОН); Д20 -78.5 (С. 0.1; Н2О-МеОН); Rf 0.75 (BAW), 0.40 (6% НОАс)

Маss-spectrum, m/z, %: 491 (20), 329 (15), 315 (30), 300 (70),167 (5), 152 (10), 134 (13), 52 (5). 1Н NMR (300 МHz, СD3OD, , ppm., J/Hz): 7.97 (1Н, d, J=2.0, Н-2); 7.76 (1Н, dd, J1=2.0, J2 =8.0, Н-6); 7.05 (1Н, d, J=8.0, Н-5); 6.35 (1Н, d, J=2.0, Н-8); 6.20 (1Н, d, J=2.0, Н-6); 5.40 (1Н, d, J=7.0, Н-1); 3.90, 3.95 (6Н, s, ОСН3). UV-spectrum, max (СН3ОН), nm: 269, 348; СН3COОNa 271, 348; СН3COОNa+H3BO3 268, 344; СН3ОNa 269, 343, AICI3 295, 360; AICI3/HCI 292, 360.

Potassium salt 3O-sulphate of 5,7,3trihydroxy-4methoxy-flavon (32), m.p. 320-322 oС (Н2О-acetone); Rf 0.55 (BAW), 0.55 (6% НОАс)

UV-spectrum, max (СН3ОН), nm: 255, 346; СН3COОNa 275, 360; СН3COОNa+H3BO3 253, 350; СН3ОNa 275, 370; AICI3 266, 360; AICI3/HCI 265, 365.

Investigation of Alcohols Compounds 3, 26 33 were isolated from ethyl acetate and water extracts. They are identified as gentrioctane-12-ol (3), trans-coniferyl alcohol (26), 4-O-sulphate of trans-coniferyl alcohol (33) accordingly on the basis of physical and chemical constants, in comparison with the literature data. Earlier these compounds were isolated from another species of Tamarix by other researchers.

32

Biological activity of genus Tamarix (T. hispida and T. ramosissima) For the first time we studied the biological activity of Kazakh species T. ramosissima and T. hispida. 13 different extracts and 4 individual compounds were tested (in vitro) in specialized laboratories of HEJ Research Institute of Chemistry, University of Karachi. 9 extracts possess enough high antibacterial, antifungal, growthregulating, antioxidant, antivirus, antidiabetic (-glucosidase), antiamnezine (PEP-inhibition), anticancer activities. From ethyl acetate extracts of T. ramosissima and T. hispida which have high antioxidant and anticancer activities, four compounds were isolated – isotamarixen, rhamnocetrin, isorahmnetin, tamarixetin and fraction of hydrolyzable tannins.Individual substance isotamarixen and fraction of hydrolyzable tannins have shown high antioxidant activity, compounds rhamnocetrin, isorahmnetin were found to be inactive. Based on this study, the phenolic hydroxyls present in the molecule seem to have an important contribution in the activity. Isotamarixen, rhamnocetrin, isorahmnetin also have high antiamnezine (PEP-inhibition) and tamarixetin – anticancer activities. Antioxidant, antiamnezine (PEPinhibition), anticancer activities of compounds 20, 20а, 22, 24 and 25 are shown in the Table 3. According to our knowledge, this is the first report of a triterpene that showed potent inhibitory activity against PEP. Many PEP inhibitors have synthesized as candidate for the treatment in neuropathological disorders but PEP inhibitors have rarely been investigated from plant material. Antidiabetic (-glucosidase), antiamnezine (PEP-inhibition) and growth stimulator activities have been shown for the first time for families Tamaricaceae.

33

Table 3 Antioxidant, Antiamnezine (PEP-inhibition), Anticancer Activities of Compounds 20, 20а, 22, 24 and 25 Compound / Standard

Compound 20 Compound 20а Compound 22 Compound 24 Compound 25 Bacitracin Propyl gallate Streptogenine

Inhibition concentration IC50 (µM) Antioxidant activity PEP enzyme inhibition DPPH Superoxide Scavenging scavenging activity activity 290.50 3061.40 0.2500.021

Zone inhibition (mm) S. cerviacae RAD 52 -

No inhibit. No inhibit.

No inhibit. No inhibit.

32.640.84

-

No inhibit.

No inhibit.

18.940.25

-

No inhibit.

No inhibit.

-

141

300.27 -

1061.70 -

129.263.28 -

281

Conclusion Following conclusions were drawn from the results  The quantitative composition of biological active complexes and elemental analyze was determined.  The schemes of separation of compounds have been elaborated. As a result, 26 compounds among them 6 phenolic acids, 11 flavonoids, 4 terpenoids, 2 hydrolizable tannins, 2 cinnamoyl and 1 long chain alcohols have been isolated. Four phenolic acids were identified by HPLC method. The structures of individual compounds were established by chemical and spectral methods.  Ten compounds are new for genus Tamarix, twelve – for T. ramosissima and T. hispida.  For the first time, a new compound 3--3,4-Dihydroxi-transcinnamoyl-оxi-D-fridoolean-14-еn-28-оic acid (isotamarixen) was isolated which has not been described in literature earlier. The structure of this compound was determined by chemical and spectral methods. 34

By means of alkaline hydrolysis, we obtained a new compound – 3оxi-D-fridoolean-14-еn-28-оic acid (epialeuritolic acid) characterized on the basis of spectral data and reported for the first time as well.  The bioassay screening of 13 extracts and 4 individual compounds showed antimicrobial, antifungal, antivirus, anticancer and antioxidant activities. For the first time, antidiabetic (-glucosidase), antiamnezine (PEP-inhibition) and growth stimulator activities have been found for the genus Tamarix.

Biological Active Compounds from Halostachys caspica, Halocnenum strobilaceum, Suaeda physophora and Suaeda microphylla A .F. Miftahova, V. U. Ahmad, G. S. Burasheva, and Z. A. Abilov The object of investigation – aerial part of Halostachys caspica, Halocnenum strobilaceum, Suaeda physophora, Suaeda microphylla belongs to Chenopodiaceae family growing in the various regions of Kazakhstan.

For obtaining biologically active compounds, the plants were extracted by chloroform, ethylacetate, acetone, water alcohol (with different concentration). The majority of biologically active compounds were extracted by 70% water alcohol solution then by chloroform, which led to obtain coumarins. For preliminary separation of phenolic compounds, extracts were consecutively processed by organic solvents to different polarity (either, ethylacetate, buthanol). In ether extract phenolic acids, ethylacetate and buthanol – flavonoids were found. For separation of flavonoids, coumarins, sterols and their glycosides used column chromatography on silica gel, as eluents chloroform, methanol and ethylacetate with different concentration. For separation of some di -, triglicosides of flavonoids chromatography was performed on polyamides as eluents water with increasing concentration of ethanol and methanol. Flavonoids of Halostachys caspian In 70% water-alcohol extracts of Halostachys caspian by using twodimensional paper chromatography established 6 phenolic acids, 6 flavonoids. By fractionations with chloroform, ethylacetate, eather, buthanol were preliminary separated from complex biologically active compounds. From ethylacetate extracts on polyamides were isolated 1 -4. Compounds 1 and 2 – yellow crystals with m.p. 216-219 and 210212 oС. In position on paper chromatograms the compounds 1 and 2 are glycoside forms of flavonoids for that acid hydrolysis was employed. By comparing reliable samples in water level for compound 1 glucose and rhamnose were identified, 2 – glucose and arabinose were identified. 36

Results obtained in the stages of hydrolysis gave intermediate product and biose for both of compounds. After 20 minutes of acid hydrolysis for 1 rhamnose was identified and for 2 at 10 minutes – arabinose was identified. At 80 minutes of hydrolysis the disappearance of biose occured and in products of hydrolysis of compounds 1 and 2 glucose appeared. The presence of biose in the product of acid hydrolysis indicated that both sugars in the compounds can be in one position of aglicone. Besides, hydrolysis on time indicates that glucose directly joined to aglicone second sugar is rhamnose for compound 1 and arabinose for 2. In EI spectrum of compound 2 weak molecular peak [M-611]+ and intensive peak of aglicone [M-316]+ were discovered while fragments of А and B rings [M-150]+, [M-166]+ , glucose [M-180]+ and arabinose [M150]+ were discovered. As the results of alkaline destruction, UV-, IRand NMR-spectrum indicate that aglicones of compound 1 are flavone – chrisoeriol and for compound 2 – flavonol – isorahmnetin. Date of IR spectrum, results of fermentation hydrolysis with rhamnodiastase, , -amylase of compounds 1 and 2 indicate that sugars have pyranose form joined by (61) linkages. Compound 1 is identified as chrizoeriol-7-O--D-glucopyranosyl (61) --L-rhamnopyranoside and compound 2 -isorahmnetine -3-O-D-glucopyranosyl (61)- -L arabopyranoside. Compound 3 – light yellow crystals with m.p. 235-237 oС, [a]D20 -580 (c 0.05; ethanol). Presence of the optical rotation and position on chromatogram was indicative of glycoside nature of compound 3 as evidenced by acid hydrolysis in the product which obtained agliconechrizoeriol and sugar – glucose. Carbohydrate linkage was determined by UV spectrum with ionizing and making of complex additives, on velocities of acid hydrolysis which prove that sugar was found on C-7 of A ring. As a result, compound 3 was identified as 7-O--D-glucopiranoside of chrizoleriol. Compound 4 – yellow crystals with m.p. 177-179 oС, [a]D20 - 890 (c 0.05 ethanol). Having maximum absorption in UV-spectrum and positive reaction with flavonoids compound 4 is referred to flavonol glycosides. Low value Rf in system BuOH: HOAc:H2O (4:1:5) and high Rf in system 15% acetic acid on paper chromatogram indicate that 37

compound is triglycoside. Acid hydrolysis had shown that аglicone is isorhamnetine but sugar components contain glucose, аrabinose and rhamnose. As a result of occurrence of hydrolysis in different stages for 20 minutes аrabinose and intermediate diglycoside were discovered and after 40 minutes rhamnose and intermediate monoglycoside were discovered, for 60 minutes – glucose but for 120 minutes of hydrolysis – aglicone, arabinose, rhamnose and glucose were determined. In UV-spectrum of compound the absence of bathochromic shift with acetate sodium and disappearance of bathochromic shift accompanied with ZrOCl3 / citric acid indicate that sugar moiety is found C-3 and C-7 positions. As a result , at fermentation hydrolysis, alkaline destruction of aglicone, UV, IR-spectrum occurring in the stages of acid compound 4 is 3-O –  – D – glycopiranosile (61)- O – --L -аrabopyranoside – 7 – O –  – L – rhamnopyranoside – 5,4' – Dihydroxy – 3' – methoxyflavone was produced which is isolated for the first time from family Chenopodiaceae. OCH3 HO

O CH3 OH

OH

O

O

O

OH HO

H2C

OH O OH

O

O

O

OH HO OH

OH

Flavonoids of Halocnenum strobilaceum In 70%-water-alchohol extract by using two-dimensional paper chromatogram in system BuOH-acetic acid-water 4:1:5 and 15%-acetic acid 5 phenolic acids and 7 flavonoids were identified. Compound 5 – yellow powder with m.p. 214-216 oС. On position on chromatogram and maximum in UV-spectrum compound 5 is referred to derivatives of flavonoid. As a result of alkaline destruction monometoxy derivative of fluroglicine and vanilic acid were identified. The two singlet signals in the field of 3.77 ppm and 3.89 ppm (s, 3H each) in NMR spectrum, absence of bathochromic shift with acetate 38

sodium and boric acid in UV spectrum confirmed that one methoxy group is found at C-3' position of B ring and second joined in C-7 position of ring A. Formation of bathochromic shift with chloride aluminum which is saved at the addition of the HCl led to the presence of free OH group in C-5 position of ring А and C-3 position of ring C. On the basis of chemical and spectral result and compared with the literary data compound 5 is identified as 7,3'-Dimethoxy- 3,5,4'trioxyflavone. OCH3 O

H3CO

OH OH

OH

O

Compound 6 – light yellow-green colorless powder with m. p. 196198 oС, Rf 0.95 (BuOH-HO Ac-water, 4:1:5) on position of the chromatogram compound is referred to methoxy aglycone. In NMR spectrum signal at 1.88 ppm, singlet led to point that compound 6 С-methylated. As it is known that typical particularity of NMR-spectrum of С-methylated compounds is the signal Ar-CH3 groups (s) which are situated in the field of 2.0-2.2 ppm moreover singlet with intensity in 3Н besides, C-6 of A ring shifted in a more strong field in contrast with proton methyl groups which can be next to C-8 of ring A. So small shift with chloride aluminum in UV spectrum (+26), signal at 1.88 ppm indicates that methyl group is found at C-6 position of ring A. In addition to this, results of alkaline destruction, signals at 3.68 ppm (6Н, s); 3.67 ppm (3Н, s) have shown that aglicon has three methoxy groups. EI spectrum has picked 162, 121, 91 and fragmentation ion (M-28) the formation is given below:

39

H3CO

O

OCH3 OCH3

H3C OH

O

H3CO

O

H3C

C

+ OH M 180

H2C

OCH3

O M 121 - M 30

M 162

M 28

M 91

On the basisof above mentioned results for compound 6 identified structure is 5 – oxy – 3,7,41 – Trimethoxy – 6 – methyl – flavonol. Flavonoids of Suaeda physophora and Suaeda microphylla Compounds 7 and 8 – light yellow powder with m.p. 212-213 oС and 234-235 oС, have a dark fluorescence in UV-light. They are glycoside in nature because of position on two-dimensional paper chromatogram and date of optical rotation. Results of acid hydrolysis and periodate oxidation describe that aglicone of compound 7 is kaempferol and for 8isorhamnetine, sugar moiety of compounds 7 and 8 is rhamnose. In products of alkaline destruction of aglicone of 7 and 8 are installed such that ring A of both compounds has a structure of fluroglicine and ring B of 7 determined as a p-оxybenzoic acid, for compound 8 – isovanillic acid. In NMR-spectrum of compound 7 signal at 0.80 ppm (s. 3H) and five signals in the field at 3.20-4.96 ppm (d) confirm the presence of the fragment of rhamnose. Two doublets of the signal in the field 6.26 – 6.67 ppm with constant meta corresponded to the signal of ring А. Two doublets at 6.86 ppm and d 7.85 ppm confirm the presence of 4' substitutions in ring B. In NMR-spectrum of compound 8 signals of 1.1ppm (3H, s) were discovered, pertaining to methyl group of rhamnose, other signals of sugar moiety in the field 3-4 ppm, anomeric protone at d 5.1 ppm of rhamnose typical exactly of 7-О- substitutions of flavonols. By twodimensional correlation spectrum, it proves that rhamnose is joined at C-3 position. 40

Compound 7 is characterized as 3 – O –  – L –rhamnpyranoside kaempferol, compound 8 is 7 – O –  – L – rhamnopyranoside isorahmnetine. Compounds 9 and 10 – pigmented and UV- light absoption with m.p. 174-176 oС and 178-180 oС. Data of chromatographic behaviors, maximum in UV-spectrum showed that compounds are flavonol glycoside. As a result of occurrence of acid hydrolysis in different stages at a time it is found that compound 9 has isorahmnetine, glucose and rhamnose. To determine of the position of the joining sugars 2D spectrum HMBC was used. The spectrum revealed that 9 is bioside, glucose is joined directly to aglicone on position C-3, but rhamnose 16 relationship is joined to glucose. Hence compound 9 was thus identified as 3 – О –  – D – glucopyranosyl (61) –  – L – rhamnopyranoside isorahmnetine. The occurrence of acid hydrolysis in different stages of compound 10 rhamnose was found, monoglycoside after 10 minutes, and glucose with aglicon after 30 minutes. It suggests that rhamnose should be attached at C-3 and glucose at C-7 positions. In UV-spectrum of compound 10, chloride aluminum and acetate sodium shift did not exist therefore, at positions C-3, C-5 and C-7 are substituted with boric acid in the absence of o-dioxy groups in ring B. After acid hydrolysis compound 10 shown with acetate sodium shift (+15 nm) on the second band it indicates that free OH group in position C-7, which is linked with glycoside. In NMR spectrum signals were found at 6-8 ppm 7.95 (d, 1H, J=2 Hz, C-2'), 7.63 (dd, 1H, J=2 Hz, 7 Hz, H-6'), 7.10 (d, 1H, J=2 Hz, H-8), 6.21 (d, 1H, J=2 Hz, H-6). The signals at 3.95 ppm (s, 3H) and 3.61 m.d. (s, 3H) belong to methoxy groups; two anomeric proton signals at 5. 23 ppm (s, 1H), 5.4 ppm (1H, d, J= 7.5 Hz) and at 1.6 ppm (d, 3 H, J=6.3 Hz, СН3) belong to two glycosides. Compound 10 determines the structure 3 – 0 –  – L – rhamnopyranosyl– 7 – О –  – D – glucopyranoside 4' – hydroxyl-5, 3' – dimethoxyflavonol.

41

C H2O H O

O

7

o

A

OH OH

8

OH

6

C

4'

B

3 O

5 OCH3

2

OCH3

3'

2'

6'

O

OH

5'

O OH

OH CH3

OH

Compounds 11 and 12- yellow crystals with m.p. 218-219 oС and 188-189 oС. The behavior on chromatograph and optical rotation indicate that compounds are flavonol diglycosides. After hydrolyses of both compounds quercetin, glucose and rhamnose were identified. The position of linked sugars moiety was determine by correlation HМВС spectrum as results have shown that glucose and rhamnose linked 61 in C-7 (compound 11) and C-3 positions (compound 12) of aglycon. The chemical and spectroscopic analyzes compound 11 established that structure as 7 – О –  – D – glucopyranosyl (6 1)  – L – rhamnopyranoside quercetin and compound 12 as- 3 – О –  – D – glucopyranosyl (6 1)  – L – rhamnopyranoside quercetin. As a result of study of plants Halostachys caspica, Halocnenum strobilaceum Suaeda physophora and Suaeda microphylla isolated 12 compounds: chrizoeriol-7-O--D-glucopyranosyl (61) --L-rhamnopyranoside; isorahmnetine -3-O- -D-glucopyranosyl (61)- -L arabopyranoside; chrizoleriol 7-O--D-glucopiranoside; 3-O – – – –D – –glycopyranosyl (61)- O – –-L -аrabopyranoside – 7 – O –  – L – rhamnopyranoside – 5,4' – Dihydroxy – 3' – methoxyflavone; 7,3'-Dimetoxy- 3,5,4'-trioxyflavone; 5 – oxy – 3,7,4' – trimethoxy – 6 – methyl – flavonol; 7 – 3 – 0- – L – rhamnpyranoside kaempferol; 7- 0 - – L – rhamnopyranoside isorahmnetine; 3 – О –  – D – glucopyranosyl (61) –  – L – rhamnopyranoside isorahmnetine; 3 – 0 –  – L – rhamnopyranoside – 7 – О –  – D – glucopyranoside 4' – hydroxyl 5, 3' – dimethoxyflavonol; 7 – О –  –D – glucopyranosyl (6 1)  – L – rhamnopyranoside quercetin; 3 – О –  – D – glucopyranosyl (6 1)  – L – rhamnopyranoside quercetin.

42

Investigation of Chloroform Extracts Halocnemum strobilaceum, Suaeda physophora, Suaeda microphylla, and Halostachys caspica The non-polar compounds were identified from chloroform extracts. In the below are shown 9 compounds which were isolated from Halocnemum strobilaceum, Suaeda physophora, Suaeda microphylla, Halostachys caspica:

Compounds nnonakosane long chain alcohol -carotine  – carotine -sitosterol stigmasterol -sitosterol glucoside Stigmasterol glucoside Oleanolic acid

Halostachys Halocnemum Suaeda Suaeda caspica strobilaceum physophora microphylla +

+

+

+

+

+

+

+

+ +

+ + + +

+ + + +

+ + + +

+

+

+

+

+

+

+

+

+

+

+

+

Coumarins of Halocnemum strobilaceum, Suaeda physophora and Suaeda microphylla, and Halostachys caspica From 70% methanol extract by using chromatography on silicagel and mixture of eluents chloroform-methanol 6 coumarins were isolated. From Halostachys caspica 1- 5 compounds were isolated: Compound 1 – white powder with m.p. 165-167 oС, in UV-light gives the violet fluorescence, in paper chromatography it looks like glicosed after acid hydrolyses glucose and aglicon-umbeliferon were obtained. In UV-spectrum bonds are found at 275, 320 nm and in IR-spectrum at 1725 cm –1 belongs to C=O group -pyrone which indicates that compound is coumarin. 43

In NMR spectrum, signals indicate СН3 – 0.87, 1.25, 1.30, 1.34 – 12Н; СН2 –2.17, 1.58, 1.48, 1.40 –8Н; СН2 = С – 4.24 –2Н; СН2- ОАr -4.9 –2Н; СН – 3.10, 3.17 –2Н which belong to terpenoid. Anomeric proton of glucose is shown at 5.10 ppm (J=2 Hz). The compound 1 determines the structure as galostarin– 12- (7'oximethelen) coumaril–17–0–α–D-glucopyranoside-12, 16, 16, 20 – tetramethyl-13- en dekalin, which is a new natural product: 5

4

6 31 C H 2 OH 29 OH

30 OH

19

12 18 20 13 17 16 21

O 26

28 27 OH

11 H2C O

O 24

25

3 7

22

8

O

O

CH2 21

14

15

Compound 2 – white crystals with m.p. 154-155oС. In NMR – spectrum signals were found: d 6.42 (d, J=9.5 Hz, H-3), 7.95 (d, J=9,5 Hz, H-4), 7.62 (dd J=1.8 8.2 Hz, H-5), 7.35 (dd, J=2.0, 7.4 Hz, H-6), 7.32 (dd, J=3.3, 7,4 Hz, H-7), 7.59 (dd, J=2.1, 8.8 Hz, H-8). In NMR 13С-spectrum shows following peaks: 162.8 (C-2), 117.1 (c-3), 145.6 (C-4), 129.4 (C-5), 125.8 (C-6), 117.5 (C-7), 133.2 (C-8), 155.3 (C-9), 120.4 (C-10). The results of NMR spectrum compared with the literary data identify the compound 2 coumarin. Compound 3- white powder with m.p. 181-182 oС, []d22 +21.410 (с 0.1; СН3ОН), Rf = 0.65 (chloroform:methanol, 98:2). In EI mass spectrum peaks are shown: 176 (М+ , 71%), 148 (100%). In NMR 1Н spectrum peaks found are: d 2.2 (s, 3H, CH3), 5.89 (s, 1H, H-3), 6.57 (d, J=3 Hz, 1H, H-8), 6.63 (dd, J=3, 11 Hz, 1H, H-6), 7.3 (d, J=11 Hz, 1H, H-5). The basis of above mentioned physico-chemical characteristic compound 3 is  -methyl – umbelliferone. Compound 4 – white powder with m.p. 181-182oС, Rf= 0.48 (chloroform: methanol, 95:5). In NMR 1Н spectrum peaks found at: d 0,88 (d, J=6.8 Hz, 3H, CH3), 1.16 (d, J=6.9 Hz, 3H, CH3), 2.34 (m, 1H, CH), 44

4.67 (d, J=3.9 Hz, CH), 6.35 (d, J=9.6 Hz, 1H, H-3), 7.97 (d, J=9.6 Hz, 1H, H-4), 7.90 (s, 1H, H-5), 7.18 (s, 1H, H-8). The signals in the low region in NMR spectrum at 6.35, 7.97, 7.90, 7.18 ppm has shown 6,7 – substituted structure of coumarins skeleton; two 3H s in 0.88, 1.16 ppm, 1H m 2.34 ppm and d 4.67 ppm belong to chain with two methyl groups. In 13С NMR -spectrum peaks were at found are : 161.5 (C-2), 115.1 (C-3), 145.6 (C-4), 125.7 (C-5), 120.2 (C-6), 175.4 (C-7), 101.5 (C-8), 162.0 (C-9), 116.2 (C-10), 201.4 (CO), 92.2 (CH), 32.3(CH), 18.8 (CH3), 16.0 (CH3). In 13С NMR – spectrum peaks were found of quaternary carbon, С=О at 201.4 ppm while other belong to carbons of coumarins nature. There were signals in mass spectrum 244 (М+, 28%), 202 (100%), 188 (24%), 187 (25%), 160 (23%). The peak of the molecular ion at 244 following molecular formula С14Н12О4. The thin structure of 4 was determine by НМВС which had shown correlation between С=О group (201.4 ppm) and С-6 (120.2 ppm) and СН (92.2 ppm) as well; two СН3-groups correlated with СН (32.2 ppm). In conclusion on the basis of NMR , mass-, НМВС –spectrum compound 4 has been identified as orsozolone:

O

CH 3

4

5

CH 3

9

6

O

7

10 8

3

O

O

Compound 5 – colorless crystals with m.p. 175-176 oС, Rf = 0.45 (chloroform-methanol, 93:7). In mass-spectrum following signals were noted: m/z 286 (M+, 22%), 202 (15%), 85 (87%), 59 (100%). The molecular peak of ion at m/z 286 following formula С16Н14О5. In IR- spectrum signals of methane group were found at 3040 – 3000 cm-1, epoxy – 1250 and 950-810 cm-1. In 1Н NMR spectrum the compound has shown signals: 1.31(s, 3H, CH3), 1.36 (s, 3H, CH3), 3.29 (d, J=3.8 Hz, 1H, OCH2-CH), 4.44 (dd, J=3.8, 45

11.0 Hz, 2H, OCH2), 4.77 (dd, J=7.0, 11.0 Hz, 2H, OCH2), 6.31 (d, J=9.6 Hz, 1H, H-3), 7.18 (dd, J=1.0 and 2.4 Hz,1H, H-5), 7.20 (d, J=2.4 Hz, 1H, a-H furan), 7.81 (d, J=2.4 Hz, 1H, b-H furan), 8.35 (dd, J=0.5 and 9.1 Hz, 1H, H-4). In NMR 13C-spectrum: 163.3 (C-2), 113.7 (C-3), 141.2 (C-4), 105.8 (C5), 115.0 (C-6), 154.2 (C-7), 108.7 (C-8), 155.3 (C-9), 149.0 (C-10), 105.8 (bC furan), 95.1 (a-C furan), 72.3(CH2), 62.8 (C-1 lactone), 60.0 (C-2 lactone). In HMBC spectrum correlation signals were found at 95.1 ppm and 105.8 ppm furan ring with С-6 115.0 ppm coumarin ring; two СН3 groups 62.8 ppm and 60.0 ppm with СН (epoxy). Therefore, compound 5 was identified as geraclenine.

6

4'

5

9

4 3

3'

5'

O

2' 7

8

10

OCH2

O

O

CH

CH3 C

O

CH3

From Halocnemum strobilaceum three compounds isolated were: coumarin, -methyl of umbelliferone and compound 6. Compound 6 – white powder with m.tp. 167-168 oС, Rf = 0.38 (chloroform-methanol, 95:5). In mass spectrum the peak with 176 (М+ – 71%) following molecular formula С10Н8О3. In NMR 1Н spectrum signals were found at 2.4 (d, J=1.2 Hz, 3H, CH3), 6.08 (dd, J=1.2, 2.3 Hz, 1H, H-4), 6.68 (d, J=2.3 Hz, 1H, H-8), 6.80 (dd, J=2.3, 8.7 Hz, 1H, H-6), 7.58 (d, J=8.7 Hz, 1H, H-5). In NMR 13С had shown peaks at 19.2 (CH3), 162.8 (C-2), 113.9 (C-3), 111.4 (C-4), 127.3 (C5), 114.5 (C-6), 164.1 (C-7), 103.7 (C-8), 156.4 (C-9), 155.8 (C-10). By using НМВС spectrum correlation it was found that protons methyl group with carbon at C-3. On the basis of spectral analyzes compound 6 has been identified as 7-hydroxy – 3 –methyl coumarin. 46

5 6

HO

7

8

9

10

4

O

3

CH3

O

From Halocnemum strobilaceum, Suaeda physophora, Suaeda microphylla, Halostachys caspica coumarins that were isolated and identified were: galostarin– 12-(7'-oximethelen) coumaril–17–0–α–D-glucopyranosido12, 16, 16, 20 – tetramethyl-13- en dekalin; coumarin;  -methyl – umbelliferone; orsozolone; geraclenine; 7-hydroxy – 3 –methyl coumarin.

Bioassay of Extracts from Halocnemum strobilaceum, Suaeda Physophora, Suaeda microphylla and Halostachys caspica A. F. Miftahova, A. Dar, A. U.Vikar, G. S. Burasheva, and Z. A. Abilov In this study, we investigated the bioactivity of different extracts from Halocnemum strobilaceum, Suaeda Physophora, Suaeda microphylla and Halostachys caspica. The extracts of Halocnemum strobilaceum have shown anticancer, while Suaeda Physophora – hipertensive, Suaeda microphylla and Halostachys caspica have shown antivirus activity. Toxicity analyzes from Halocnemum strobilaceum was studied by generally accepted method of the toxicology on white mouse and rat following intraperitoneal injection. Experimental results were analyzed statistically, LD50 – for mice 610 – 640 mg / kg and for rats – 720-760 mg / kg. Chronic toxicity of the complex from Halocnemum strobilaceum in 10% in water solution is studied by experiencing it on rat with interwoven tumor in greatly exportable dose (MPD) for mice 50 mg / kg and for rats 60 mg / kg. Anticancer activity of extract from Halocnemum strobilaceum in greatly exportable dose 50-60 mg / kg accordingly decreases the growth of mucous it would be either liver cancer or mucosa cancer RS-1 (73,2%, R S3 (28.1) >>>> Standart 2 Control after 4 h

Sample 4 after 4 h

3. Treatment of Burn Wound in Rats 3.1. Preparation of aqua gel form 0.05 g of dry powder figurative polymer-clay gel with alhidine immobilized in it was added in 1 mL of water for swelling. All swelling gels were kept at room temperature for overnight. As a result soft easily applied gel forms of brown color were formed. 3.2. Preparation of cream form For a base, a cream form of Vaseline was used. 30 % creams in quantity 0 .1 g had been prepared as follows: 0 .05 g of dry powder figurative polymer-clay gel with alhidine immobilized in it was swollen in 1 mL of water and had been mixed with 0.07 g (0.05 g) vaseline. Homogeneous weight of brown color, which is characteristic to a medical product alhidine was received.

114

3.3. Design of experiment We had tested the polymer composite on a thermal burn model of rat. A local scalding was performed in order to produce burns in female Wistar rats weighing 250-300 g. Animals were housed in individual cages with unrestricted food and water access. Animals were divided in two sections: – one was treated by aqua gels of polymer-clay compositions, the other by cream form of same compositions. Each section had 13 groups and had three animals per cage (Table 4). Table 4 The design of the animal groups for burn wound treatment Animal groups 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Section treated by aqua gel form Name of animal groups Blank (without burn) Control (burn wound untreated) Standard (treated by Dermazin) [ALH] [BC-ALH] [PHEA-ALH] [PHEA-BC-ALH] [PAAM-ALH] [PAAM-BC-ALH] [PAA-ALH] [PAA-BC-ALH] [PMAA-ALH] [PMAA-BC-ALH]

Section treated by cream form Name of animal groups Control (burn wound untreated) Standard (treated by Dermazin) Vaseline [ALH-Vas] [BC-ALH-Vas] [PHEA-ALH-Vas] [PHEA-BC-ALH-Vas] [PAAM-ALH-Vas] [PAAM-BC-ALH-Vas] [PAA-ALH-Vas] [PAA-BC-ALH-Vas] [PMAA-ALH-Vas] [PMAA-BC-ALH-Vas]

Total body surface area of 6 to 7 cm was used for experimental purpose. All animals were anesthetized and were shaved on the dorsum from thorax to abdomen transversally in such a way as to spare the ventral surface of thorax and abdomen. After this, burns were induced locally using scalding method. After scalding, the test compounds were applied topically on the burns. For recovery the animals were then placed separately in clean cages supplied with water and food and were kept under observation for next 3-4 days. The animals were dressed twice a day with the test polymer composites. As standard drug the “Dermazin” cream (1% Silver Sulphadiazine u.s.p.) was used.

115

Treatment had been visually observed as seen in photos of some samples Name 1 day –before and After 3 days of after the application treatment Blank (without burn) Control (untreated burn wound)

Standard (treatment with Dermazin) [ALH]

[PHEA-BC-ALH]

[PAAM-BC-ALH]

[PAA-BC-ALH]

[PMAA-BC-ALH]

116

Synthesis of phenylacetylenic derivatives of decahydroquinoline M. Z. Turmukhanova and M. Iqbal Choudhary Synthesis of ethyl ether of 2-brom-acetic acid Ethyl ether of bromide acetic acid was obtained by the etherification of 2-brom-acetic acid with ethyl alcohol in the presence of catalytic traces of sulphuric acid. Since the etherification reaction is equal to water obtained at the result of the process it was removed from the reaction sphere by the distillation with benzene for the displacement of equilibrium in the direction of ether formation. O H

N

OH

[H]

H

CH3 1 Br-CH2COOC2H5

O N C C

OH N

C C CH3

+ H

3

CH3 2

Br-CH2COOC2H5

KOH

H

N

N

O OH

CH3

OH N

CH3

CH3

O O C2H5 6

O C2H5 5

4 Br-CH2COOC2H5

Br-CH2CH=CH2

Br-CH2CH=CH2

N

C C CH3

C C

C C

OH 3.1

N

OH CH3

4.1

OH CH3

7

O O C2H5

COCl

C C N

N

O C

O CH3

4.2

Condensation of 2 e-methyl-trans-decahydroquinoline-4-one with phenylacetylene 117

Mixture of isomers of 2e-methyl-4-phenylethinyl-4oxy-transdecahydroquinoline was synthesized by the condensation of 2e-methyl4-keto-trans-decahydroquinoline (1) in dry dioxane. Separation of isomers mixture of 2e-methyl-4-phenylethinyl-4oxy-trans-decahydroquinoline Using different solubility of acetates and hydrochlorides of corresponding isomers in isopropyl and ethyl alcohols the isomers mixture of 2e-methyl-4-phenylethinyl-4oxy-trans-decahydroquinoline was separated into individual isomers: isomer I – 2e-methyl-4aphenylethinyl-4e-oxy-trans-decahydroqinoline (4); isomer II – 2emethyl-4e-phenylethinyl-4a-oxy-trans-decahydroquinoline. Synthesis of N-carbethoxymethyl-2e-methyl-trans-decahydroquino-line-4-one N-carbethoxymethyl-2e-methyl-trans-decahydroquinoline-4-one (5) was obtained in the form of colorless needles with bp 72-73 ˚C by the alkylation of 2e-methyl-trans-decahydroquinoline-4-one (1) with ethyl ether of 2-brom-acetic acid in dry acetone in the presence of calcinated potash. Composition and structure of the synthesized compound were proved by Element Analysis, Infrared Spectroscopy, and Mass Spectrometry. Synthesis of N-carbethoxymethyl-2e-methyl-4e-oxy-trans-decahydro-qinoline N-carbethoxymethyl-2e-methyl-4e-oxy-trans-decahydroquinoline (6) was obtained in the form of colorless needles with bp 91-93°C by the alkylation of 2e-methyl-4e-oxy-trans-decahydroquinoline with ethyl ether of 2-brom-acetic acid in dry acetone in the presence of calcinated potash. Composition and structure of the synthesized compound were proved on the basis of Element Analysis, Infrared Spectroscopy, and Mass Spectrometry. IR-spectrum of N-carbethoxymethyl-2e-methyl-4e-oxy-trans-decahydөroquinoline (6) is shown in Figure 1.

118

Figure 1 –

The Infrared Spectrum of N-carbethoxymethyl-2e-methyl-4e-oxytrans-decahydroquinoline

The IR-spectrum of N-carbethoxymethyl-2e-methyl-4e-oxy-transdecahydroquinoline was taken in the form of tablet in solid KBr. There is a sharp peak of hydroxyl group at 3490 cm-1 which is characteristic of dimers. A number of peaks at 2813 cm-1, 2860 cm-1, 2927 cm-1, and 2980 cm-1 are typical of valency symmetric and asymmetric vibrations of methyl and methylene C-H bond. The absorption peak at 1449 cm-1 corresponds to deformational vibrations of methylene group. The strong peak at 1744 cm-1 corresponds to vibrations of ester’s carbonyle group. As for acids one or several intensive peaks appear at the spectra of esters at 1300-1050 cm-1 caused by the participation of ester bond C-O-C (so called “ester peak”). This absorption can be identified with high intensity. Although, “ester peak” is stronger and broader than carbonyl peak, sometimes it can be decomposed. There is a strong absorption peak at 1190 cm-1 at IR-spectrum of compound (6). This peak corresponds to “ester peak”. Structure of synthesized N-carbethoxymethyl-2e-methyl-4e-oxytrans-decahydroquinoline was also proved by Mass Spectrometry. Its data is shown in Figure 2.

119

Figure 2 – The Mass Spectrum of N-carbethoxymethyl-2e-methyl-4e-oxy-transdecahydroquinoline

In the mass spectra of compound (6), a weak molecular ion peak at m/z 255 can be observed. After the breaking apart of carbethoxy-radical (m/z 73) from molecular ion a stable fragment ion (m/z 182) with the highest intensity is formed.

OH

OH - COOC2H 5

N m/z 255 H2C (3,29%)

CH3 COOC2H 5

N m/z 182 (100%)

CH3

CH 2

The fragmention peak at m/z 240 (7.72%) is due to the loss of the methyl radical from the molecular ion. The first one transforms into ion (m/z=212) (7.08%) as a result of splitting off the neutral ethylene molecule. 120

OH

OH - CH3

N m/z 255 H2C (3,29%)

- C 2 H4

CH3 COOC2H5

OH

N

N

m/z 240 H2C (7,72%)

m/z 212 H2C COOC2H5 (7,08%)

COOH

The fragment ion with m/z=240 transforms into ion-radical with m/z=149 (7.72%) due to the loss of carbethoxy-ion and the molecule of water. Ion-radical with m/z=105 (5.81) occurs due to the loss of propane molecule from ion-radical with m/z=149. OH

OH - COOC2H5 - H2 O

N H 2C

m/z 240 (7,08%) COOC2H5

NH HC

COOC2H5

- C 3 H8

m/z 149

N CH2

m/z 105 (5,81%)

N CH2

Synthesis of N-carbethoxymethyl-2e-methyl-4a-phenylethinyl-4eoxy-trans-decahydroquinoline N-carbethoxymethyl-2e-methyl-4a-phenylethinyl-4e-oxy-transdecahydroquinoline (7) was obtained by the alkylation of 2e-methyl-4aphenylethinyl-4e-oxy-trans-decahydroquinoline (4) with ethyl ether of 2-bromoacetic acid. Composition and structure of the synthesized compound were proved by dates of Element Analysis, Infrared Spectroscopy, and Mass Spectrometry. IR-spectrum of compound (7) is shown in Figure 3. 121

The IR-spectrum of N-carbethoxymethyl-2e-methyl-4aphenylethinyl-4e-oxy-trans-decahydroquinoline was taken in the form of tablet in solid KBr. There is a sharp peak of hydroxyl group absorption at 3417 cm-1 in the IR-spectrum of compound (7) which is characteristic of dimers. Valence C-H vibrations of aromatic fragment that possess average intensity appear at 3053 cm-1. Usually they look like a group of peaks. But if there is an aliphatic chain besides an aromatic ring, absorption peaks of aromatic bonds C-H unite with absorption peaks of C-H bonds of methyl and methylene groups and look like shoulders at the main aliphatic peak С-Н. These three absorption peaks at 1599 cm-1, 1573 cm-1, and 1442 cm-1 also correspond to the absorption of aromatic fragment. The absorption peak at 2200 cm-1 with low intensity corresponds to the СС bond of phenylethinyl substitute. The strong peak at 1728 cm-1 corresponds to vibrations of ester’s carbonyl group. As for acids one or several intensive peaks appeared in the spectrums of esters at 1300-1050 cm-1 caused by the participation of ester bond C-O-C (so called “ester peak”). This absorption can be identified with high intensity. And as a rule, “ester peak” is stronger and broader than carbonyl one, and sometimes it can be decomposed. There is a strong absorption peak at 1186 cm-1 in the IR-spectrum of compound (7). This peak corresponds to “ester peak”.

Figure 3 – The IR of N-carbethoxymethyl-2e-methyl-4a-phenylethinyl-4e-oxytrans-decahydroquinoline

122

Structure of synthesized N-carbethoxymethyl-2e-methyl-4a-phenylethinyl-4e-oxy-trans-decahydroquinoline was also proved by Mass Spectrometry. Its data is shown in Figure 4.

Figure 4 – The mass-spectrum of N-carbethoxymethyl-2e-methyl-4a-phenylethinyl4e-oxy-trans-decahydroquinoline

In the mass-spectrum of compound (7), a molecular ion peak with low intensity at m/z 355 (2.53%) can be observed which forms corresponding fragment ions with m/z 340 and m/z 338 (4.11%) by loosing methyl and hydroxyl groups. Due to the loss of ethylene molecule the fragment ion with m/z 340 transforms into fragment ion with m/z 312 (2.4%). After breaking of ethylformate molecule ion with m/z 338 converts into ion with m/z 264 (2.83%). C 6H 5

C 6H 5 HO

C 6H 5

HO - CH 3

N

m /z 3 40

H 2C - C2H 4

CO O C 2 H 5 C 6H 5

- OH

N m /z 355 (7,08% ) H 2 C

CH3 C O O C 2H 5

N m /z 338 (4,11% ) H 2 C

CH3 C OO C2H5

- H C O O C 2H5

C 6H 5

HO

N m /z 312 (2,4% ) H 2 C

CO O H

m /z 264 (2,83% )

N

CH3

CH 2

123

Formation of stable fragment ion with m/z 282 (100%) having the highest intensity in the mass-spectrum was due to the loss of carbethoxy-radical from molecular ion.

C6H5

C6H5

HO

HO - COOC2H5

N m/z 355 (7,08%) H2C

CH3

N

m/z 282 (100%)

COOC2H5

CH3

CH2

Due to the loss of ethylformate from molecular ion a very unstable ion-radical with m/z 281 was formed. It decomposed into three particles: neutral molecule with 210 (2.83%), fragment ion with m/z 56 (34.69%), and radical with m/z 71 (7.33%).

C6H5 HO

C 6H 5

O

CH3

N

HO - HCOOC2H5

N m/z 355 (7,08%) H2C

CH3

m/z 281

N CH2

COOC2H5

H 3C

CH

CH2

C6H5

CH3

O N +

C6H5 m/z 210 (2,83%)

HC

CH2 +

CH3

CH3

m/z 56 (34,69%)

O

+

C6H5 m/z 210 (2,83%)

m/z 81 (7,33%)

O

C6H5 m/z 129 (27,74%)

Formed fragment ion with m/z 129 suffers a decomposition with a consecutive throwing of two molecules of acetylene and as a result two fragment ions with 103 (2.44%) and m/z 77 (5.68%) were formed.

124

O

C 6H5

O

C

C

- C 2 H2

C

m/z 129 (27,74%) O

C

C

- C 2 H2

C

O

C

C

m/z 103 (2,44%)

C

C

CH

m/z 77 (5,68%)

The fragment ion with m/z 282 broke apart and had given ionradical with m/z 149 (3.99%) and fragment ion with m/z 115 (23/19%) due to the loss of water molecule. C6H5

C6H5

HO

m/z 282 (100%)

N

CH3

N

CH2

+

N m/z 149 CH3 (3,99%)

CH3

CH2

H 2C

CH3 m/z 115 (23,19%)

Synthesis of N-allyl-2e-methyl-4e-phenylethinyl-4a-oxy-trans-decahydro-quinoline N-allyl-2e-methyl-4e-phenylethinyl-4a-oxy-trans-decahydroquinoline (4.1) was obtained by the alkylation of the 2e-methyl-4e-phenylethinyl-4aoxy-trans-decahydroquinoline (4) with bromide allyl. Composition and structure of the synthesized compound were proved on the grounds of dates of Element Analysis, Infrared Spectroscopy, and Mass Spectrometry. The IR-spectrum of compound (4.1) is shown in Figure 5. The IR-spectrum of N-allyl-2e-methyl-4a-phenylethinyl-4a-oxytrans-decahydro-quinoline was taken in the form of tablet in solid KBr. There is a sharp peak of hydroxyl group absorption at 3150 cm-1 in the IR-spectrum of compound (4.1) which is characteristic of dimers.

125

Figure 5 – The IR-Spectrum of N-allyl-2e-methyl-4e-phenylethinyl-4a-oxy-transdecahydroquinoline

Usually they look like a group of peaks. But if there is an aliphatic chain besides an aromatic ring, absorption peaks of aromatic bonds C-H unite with absorption peaks of C-H bonds of methyl and methylene groups and look like shoulders at the main aliphatic peak С-Н. The absorption peak at 2200 cm-1 with low intensity corresponds to the СС bond of phenylethinyl substitute. A weak absorption peak at 1638 cm-1 is related to valence vibrations of С=С. These three absorption peaks at 1597 cm-1, 1486 cm-1, and 1445 cm-1 also correspond to the absorption of aromatic fragment. Structure of synthesized N-allyl-2e-methyl-4e-phenylethinyl-4a-oxytrans-decahydroquinoline was also proved by Mass Spectrometry. Its data is shown in Figure 6. In the mass-spectrum of compound (4.1) a molecular ion peak with m/z 309 and 25% intensity gives an ion with m/z 292 (96%) due to the loss of hydroxyl radical. Formed ion with m/z 292 (96%) breaks apart giving an unstable ionradical with m/z 177 and an ion with m/z 115 (32.33%).

126

C 6 H5

C6H5

HO -OH N CH3 m/z 292 CH CH CH 2 2 (96,7%)

N CH3 m/z 309 CH CH CH 2 2 (25%) C 6H 5

+

N

N

CH3

m/z 292 (67,7%)

H2C

C

C

C6H5

CH3 m/z 115 (32,33%)

m/z 177

Figure 6 – The Mass-Spectrum of N-allyl-2e-methyl-4e-phenylethinyl-4a-oxytrans-decahydroquinoline

An ion with m/z 276 (5%) appears from the molecular ion with m/z 309 through the unstable ion-radical with m/z 291 by loosing a molecule of water.

C 6H 5

C 6H 5

C 6H 5

HO -H2O

N m/z 309 (25%)

N

CH3

CH2 CH

CH2

m/z 291

CH3

CH2 CH

CH2

N m/z 276H C 2 (5%)

CH

CH2

127

An intensive fragment ion peak appeared at m/z 294 (92.22%) as a result of loss of methyl radical from molecular ion. C6 H5

C 6H 5

HO

HO -CH 3

N m/z 309 (25%)

N

CH3

CH2 CH

CH2

m/z 294 (92,24%)

CH2 CH

CH2

After isomerization of propyl radical a fragment ion with 266 (100%) and the highest intensity appears due to the loss methyl radical.

C 6 H5 HO -CH2CH 2CH3

N

C 6H 5 H 2C

HO

CH3

m/z 309 (25%)

CH3

N m/z 266 (100%)

Also, the isomerization of the molecular ion with m/z 309 gives an ionradical with m/z 252 (9.73%) and allylic amine with m/z 57 (14.23%). The further electron attack splits the neutral molecule of phenylacetylene with m/z 102 (10.56%) giving off an ion-radical with m/z 150 (4.34%).

C6H5 HO

N m/z 309 (25%)

128

C 6H5 HO

CH3

CH2 CH

CH2

NH

CH3

CH2 CH

CH2

C6H5 HO NH2 +

CH2

CH3

m/z 252 (9,73%)

CH

CH2

m/z 57 (14,23%)

C6H5

O

HO

+ HC

C

CH3

CH3 m/z 252 (9,73%)

m/z 102 (10,56%)

m/z 150 (4,34%)

A fragment ion with m/z 282 (5.63%) appeared due to the loss of ethylene molecule from the molecular ion with m/z 309. The first one in its turn breaks apart into two particles with m/z 153 (2.77%) and m/z 129 (72.56%), respectively.

C6H5

C6H5

HO

HO - CH=CH2

N

CH3 m/z 282 (5,63%)

+

N m/z 153 (2,77%) CH3

CH3

N

m/z 309 (25%)

CH2

O

C6H5

CH3 m/z 129 (72,56%)

Synthesis of N-allyl-2e-methyl-4a-phenylethinyl-4e-oxi-trans-decahydroquinoline N-allyl-2e-methyl-4a-phenylethinyl-4e-oxi-trans-decahydroquinoline (3.1) was obtained by the alkylation of 2e-methyl-4a-phenylethinyl4e-oxi-trans-decahydroquinoline (3) with bromide allyl. Composition and structure of the synthesized compound were proved on the grounds of dates of Element Analysis, Infrared Spectroscopy, and Mass Spectrometry. The IR-spectrum of compound (3.1) is shown in Figure 7. 129

The IR-spectrum of N-allyl-2e-methyl-4e-phenylethinyl-4a-oxytrans-decahydroquinoline was taken in the form of tablet in solid KBr. There is a sharp peak of hydroxyl group absorption at 3150 cm-1 in the IR-spectrum of compound (3.1) which is characteristic of dimers. Valence C-H vibrations of aromatic fragment that possess average intensity appear at 3000 cm-1. Usually they look like a group of peaks. But if there is an aliphatic chain besides an aromatic ring, absorption peaks of aromatic bonds C-H unite with absorption peaks of C-H bonds of methyl and methylene groups and look like shoulders at the main aliphatic peak С-Н. The absorption peak at 2200 cm-1 with low intensity corresponds to the СС bond of phenylethynyl substitute. A weak absorption peak at 1638 cm-1 is related to valence vibrations of С=С. These three absorption peaks at 1598 cm-1, 1489 cm-1, and 1445 cm-1 also correspond to the absorption of aromatic fragment. Structure of synthesized N-allyl-2e-methyl-4a-phenylethinyl-4e-oxytrans-decahydroquinoline was also proved by Mass Spectrometry. Its data is shown in Figure 8.

Figure 7 – The IR-Spectrum of N-allyl-2e-methyl-4a-phenylethinyl-4e-oxy-transdecahydroquinoline

130

Figure 8 – The Mass Spectrum of N-allyl-2e-methyl-4aphenylethinyl-4e-oxytrans-decahydroquinoline

In the mass-spectrum of compound (3.1) a molecular ion peak at m/z 309 (11.04%) gives an ion with m/z 292 (64.06%) due to the loss of hydroxyl group.

C6H5

C6H5

HO -OH N

CH3

m/z 309 CH2 CH (11,04%)

CH2

N

CH3

m/z 292 CH CH 2 (64,06%)

CH2

Mainly the fragmentation of the molecule of synthesized N-allyl-2emethyl-4a-phenylethinyl-4e-oxy-trans-decahydroquinoline (3.1) corresponds with the fragmentation of its isomer N-allyl-2e-methyl-4eoxy-trans-decahydroquinolime. Synthesized phenylacetylenic derivatives of decahydroquinoline were directed for examining their biological activity.

131

CONCLUSION [1]. Isomers of 2e-methyl-4-phenylethinyl-4oxy-trans-decahydroquinoline were obtained by the condensation of -trans-decahydroquinoline-4-one and phenylacetylene in the presence of dioxane. [2]. N-allyl-2e-methyl-4e-phenylethinyl-4a-oxy-transdecahydroquinoline was synth-esized by the alkylation of 2e-methyl4e-phenylethinyl-4a-oxy-trans-decahydroquinoline with bromide allyl and on the basis of mass-spectrum data its structure was studied in detail; [3]. N-allyl-2e-methyl-4e-phenylethinyl-4a-oxy-transdecahydroquinoline was synthesized by the alkylation of 2e-methyl-4aphenylethinyl-4a-oxy-trans-decahydroquinoline with bromide allyl; on the grounds of mass-spectrum dates its structure was studied in detail; [4]. N-carbethoxymethyl-2e-methyl-4e-phenylethinyl-4a-oxy-transdecahydroquinoline was obtained by the alkylation of 2e-methyl-4ephenylethinyl-4a-oxy-trans-decahydroquinoline with ethyl ether of 2brom-acetic acid and on the grounds of mass-spectrum data its structure was studied in detail; [5]. N-carbethoxymethyl-2e-methyl-trans-decahydroquinoline-4-one was synthesized by the alkylation of 2e-methyl-trans-decahydroquinoline-4-one and on the grounds of mass-spectrum data its structure was studied in detail; [6]. N-carbethoxymethyl-2e-methyl-4e-oxy-trans-decahydroquinoline was synthesized by the alkylation of 2e-methyl-4e-oxy-trans-decahydroquinoline with ethyl ether of bromide acetic acid on the grounds of mass-spectrum dates its structure was studied in detail; [7]. Synthesized compounds were directed for examining their biological activities.

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Research Publications 1999 year [1]. Abilov Zh.A., Gladyshev P.P., Adekenov S.M., Atta-ur-Rahman, Choudhary M. I., Project for establishing of integrated information system in the field of phytochemistry, pharmacology and medicinal chemistry // International Conference “Medicinal raw material and phytopreparation for medicine and agriculture”. – Karaganda, 1999. – P. 96-97 2000 year [1]. Miftakhova A.F., Ahmad V.U., Zahid M., Burasheva G.Sh., Abilov Zh. A. Coumarins from the aerial part of Halocnemum strobilaceum // Fitoterapia, 2000.-Vol. 72.- P.319-321. [2]. Pak R.N., Dar A., Miftakhova A.F., Atta-ur-Rahman, Burasheva G.Sh, Abilov Zh.A., Adekenov S.M., Rahimov K.D. Gipertenzive activity of water exctract Suaeda physophora // In abstract of scientificpractic conference, initiation 60 year’s for M.N. Muhametzhanov, Каraganda, 2000.- Р.145-147. 2001-2003 years [1]. Sultanova N., Makhmoor T., Abilov Zh.A., Omurkamzinova V.B., Atta-ur-Rahman, M.I.Choudhary. Antioxidant and antimicrobial activities of Tamarix ramosissima // Journal of Ethnopharmocology, 2001.-Vol.78.-P.201-205 [2]. Sultanova N.A., Abilov Zh.A., Omurkamzinova V.B., Choudhary M. I. Iqbal. Flavonoids from aerial part of Tamarix hispida family Tamaricaceae // Chemistry of natural compounds, 2002, №1, P.80 [3]. Sultanova N., Makhmoor T., Abilov Zh.A., Omurkamzinova V.B., Atta-ur-Rahman, M.I.Choudhary. The genus Tamarix –potential source of bioactive compounds // In abstract of International scientific conference “Chemistry, Technology and Medicinal aspects natural products. – Almaty, Kazakhstan, 2003, p.133 [4]. Yeskalieva B.K., Burasheva G.Sh., Choudhary M.I., Abilov Zh.A. Oil acids and pharmacological activity of Climacoptera // Pharm. bull. – 2003. – № 11. – P. 37-38 (In Rus). 2004 year [1]. Korulkina L.M., Zhusupova G.E., Shulc E.E., Abilov Zh.A., Erzhanov R.B., Choudhary M.I. Bioactive compounds of Limmonium 133

Gmelini and Limonium Popovi (Plumbaginaceae). Report 1 // Chemistry of natural compounds, 2004.-№5.-P.383-387. [2]. Karzhaubekova Zh.Zh., Siddiqui B.S., Burasheva G.Sh. Triterpnoids of genus Kalidium // In abstract of international conference “Chemistry and using natural and synthetically bioactive compounds” . – Almaty, 2004. – P.116-119 (In Rus.). [3]. Sultanova N.A., Umbetova A.K., Choudhary M.I., Omurkamzinovа V.B., Abilov Zh.A., Atta-ur-Rahman. Polyphenol constituents of Tamarix. // In abstract of 9-th International symposium on Natural Product Chemistry. – Karachi, 2004. – P. 320. [4]. Sultanova N., Makhmoor T., Yasin A., Abilov Zh.A., Omurkamzinova V.B., Atta-ur-Rahman, Choudhary M.I. Isotamarixen-A New Antioxidant and Propyl Endopeptidase-Inhibiting Triterpenoid from Tamarix hispida // Planta Medica, 2004, 70 (1), P.65-67. [5]. Sultanova N., Makhmoor T., Abilov Zh.A., Atta-ur-Rahman, Choudhary M.I. Terpenoids of Tamarix Hispida // International Conference on Natural Products and Physiologically Active Substances (ICNPAS-2004), September 12-17, 2004, Novosibirsk, Russia, p.114. [6]. Yeskaliyeva B.K., Karzhaubekova Zh.Zh., Turtaeva G.O., Burasheva G.Sh., Ahmad V.U., Abilov Zh.A. Phytochemical investigation of some plants of family Chenopodiaeceae // In abstract 9 th International Symposium of natural product chemistry. – Karachi, 2004. – P.335. [7]. Yeskaliyeva B.K., Ahmed A., Burasheva G.Sh., Ahmad V.U., Abilov Zh.A. Biological active compounds from Climacoptera // Chemistry of natural compounds – 2004. – №1. – P. 76-77. [8]. Yeskaliyeva B.K., Karzhaubekova Zh.Zh., Turtaeva G.O., Burasheva G.Sh., Ahmad V.U., Abilov Zh.A. Phytochemical investtigation of some plants of family Chenopodiaceae // In abstract of 9-th International Symposium on Natural Product Chemistry. – Karachi, 2004. – Р. 335. [9]. Yeskaliyeva B.K., Ahmed A., Burasheva G.Sh., Choudhary I.M., Abilov Zh.A. Phytochemical investigation of genus Climacoptera // In abstract of international conference “Chemistry and using natural and synthetically bioactive compounds”. – Алматы, 2004. – P. 113 -115 (In Kaz.). 134

[10]. Umbetova

A.K., Esirkegenova S. Z., Choudhary M.I., Omurkamzinovа V.B., Abilov Zh.A. Flavonoids of genus Tamarix // Chemistry of natural compounds. – 2004. – № 3. – P. 250. 2005 year [1]. Korulkina L.M., Zhusupova G.E., Shulc E.E., Abilov Zh.A., Erzhanov R.B., Choudhary M.I. Fitosterols of two species of Limonium // Vestnik KazNU, 2005.-№1.- P.24-29 (In Rus.). [2]. Umbetova A.K., Dik E.P., Choudhary M.I., Sultanova N.A., Burasheva G.Sh., Abilov Zh.A. Investigation amino-, fatty-, phenolic acids of Camphorosma monspeliacum // Pharm. bull.-2005.-№3. -P.24- 26 (In Rus.). [3]. Umbetova A., Choudhary I.M., Burasheva G.Sh., Sultanova N.A., Abilov Zh.A. Biological active compounds from Camphorosma monspeliacum // Chemistry of natural compounds, № 6, 2005, P. 598-599. [4]. Umbetova A., Choudhary I.M., Burasheva G.Sh., Sultanova N.A., Abilov Zh.A. Flavonoids of genus Tamarix II // Chemistry of natural compounds, № 6, 2005, p.600-601. 2006 year [1]. Siddiqui B.S., Karzhaubekova Zh.Zh., Burasheva G.Sh., Sultanova N.A. Two new antibacterial triterpenes // In abstract of 10-th International Symposium of natural product chemistry. – Karachi, 2006. – P.201. [2]. Siddiqui B.S., Karzhaubekova Zh.Zh., Burasheva G.Sh., Sultanova N.A. Triterpenoids from the Aerial Parts of Kalidium foliatum, Helvetica Chimica Actа. – 2006. – Vol. 89 – P. 969-982. [3]. Umbetova A., Choudhary I.M., Sultanova N.A., Burasheva G.Sh., Abilov Zh.A. Triterpenoids of genus Tamarix // Chemistry of natural compounds, №3, 2006, p.173-176. [4]. Yeskaliyeva Balakyz., Ahmed M. Mesaik., Ahmed Abbaskhan., Aisha Kulsoom., Burasheva G.Sh., Abilov Zh.A., M. Choudhary M. I.., Atta-ur-Rahman. Bioactive flavonoids and saponins from Climacoptera obtusifolia // Phytochemistry. – 2006. – Vol. 67, No. 21. – P. 2392-2397. [5]. Yeskalieva B.K., Choudhary I.M., Sultanova N.A., Burasheva G.Sh., Abilov Zh.A. Biological active compounds of Climacoptera // Pharmaceutical bulletin, № 1-2, 2006, p.57-59 (In Rus.). 135

[6]. Zhenis Zh., Yeskalieva B.K., Choudhary I.M., Burasheva G.Sh.,

Abilov Zh.A. Phytochemical analyses of two species of genus Atriplex and pharmacological activity // Pharmateutical bulleten. – 2006. – № 12. – P. 55-56 (In Rus.). 2007 year [1]. Kudaibergenova, B.M., Zhumagalieva, Sh. N., Beisebekov, M.K., Abilov, Zh.A., Choudhary, M.I. Self-Structured Supports on a Base of Organic-Mineral Composite Materials for Medical Compounds // II International conference on natural products: Chemistry, technology and medicinal perspectives. – 2007. – Almaty, Kazakhstan. – P. 151. [2]. Kudaibergenova, B.M., Zhumagalieva, Sh.N., Beisebekov, M.K., Abilov, Zh. A., Choudhary, M.I. Studying of composite systems on a basis of bentonitic clay and gelatin // News of scientific and technical society "Kahak". – 2007 – p. 205 (In Rus.). [3]. Kudaibergenova, B.M., Zhumagalieva, Sh.N., Beisebekov, M.K., Abilov, Zh.A., Chaudhary, M.I. Clay compositions of polyvinyl alcohol for immobilization and alchidine // News of the National Academy of sciences of the Republic of Kazakh – 2007. – №4. – p. 75-79 (In Rus.). [4]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B, Choudhary M. I., Mesaik M. Ahmed. Study antibacterial of activity of extracts: Reaumuria soongаrica (pall). maxim. and Tamarix arceuthoides bgе // of News of a scientific and Technical society (community) "Kahak". Materials III of the International scientific conference " Modern lines of development of a science in central Asia ". – Almaty, 2007 (17). – P. 81-82 (In Rus.). [5]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B, Choudhary M. I., Mesaik M. Ahmed. Immunomodulatory studies of crude extracts of Reaumuria soongаrica and Tamarix arceuthoides // Abstracts book the III International Scientific Conference " Modern Tendencies of Development of Science in Central Asia ". – Almaty, 2007.- P. 221-222. [6]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B, Choudhary M. I. Study of chemical properties of biologically active substances and biological activity Таmarix arceuthoides Вge. and Reaumuria soоngоrica (Pall). Maxim.// Innovation development of a science in modern Kazakhstan: materials of a Republican scientific – 136

practical conference: chemical sciences: the collection of clauses. – Almaty, 2007. – P. 167 -169 (In Rus.). [7]. Siddiqui B.S., Karzhaubekova Zh.Zh., Burasheva G.Sh., Sultanova N.A. Сhemical Constituents of the Aerial Parts of Kalidium foliatum // Chem.Pharm.Bull. – 2007. – Vol. 55 (9) – P. 356 – 360. 2008 year [1]. Kudaibergenova, B.M., Zhumagalieva, Sh.N., Beisebekov, M.K., Abilov, Zh.A., Chaudhary, M.I. Composites carriers on the basis of bentonit clay and polysaccharides // Journal of applied chemistry. 2008. V. 81. Issue 6. P. 1005-1008. [2]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B, Choudhary M. I. Polyphenolic compounds Tamarix arceuthoides Bge. //Chemical magazine of Kazakhstan. Almaty, 2008. № 1. P. 280 -283 (In Rus.). [3]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B, Choudhary M. I. Polyphenolic compounds Reaumuria soongаrica (pall). maxim // Chemical magazine of Kazakhstan. Алматы, 2008. № 1. P. 275 -280 (In Rus.). [4]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B, Choudhary M. I. Study of biological activity of extracts of plants Reaumuria soongаrica (Pall). Maxim. and Tamarix arceuthoides Bge. // The Bulletin Treasury Kazak National University named after al’-Farabi. A series chemical. Almaty 2008. № 1 (49). P. 13-15(In Rus.). [5]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B, Choudhary M. I. Biologically active substances Reaumuria soongarica and Tаmarix arceuthoides // Chemistry and chemical technology of vegetative substances: materials Y the All-Russia conference – school. – Ufa, June 8-12 2008. P. 217. [6]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B, Choudhary M. I. Biologically active substances Reaumuria soongarica and Tаmarix arceuthoides. // Chemistry and chemical technology of vegetative substances: materials Y the All-Russia conference – school. – Ufa, June 8-12 2008. P. 217. [7]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B, Choudhary M. I.. Seitembetova A.Zh. Antioxidant activity of extracts from Reaumuria soоngаrica (pall). maxim. // Chemistry and chemical technology of vegetative substances: Y the All-Russia Conference – school. – Ufa, June 8-12 2008. P. 218. 137

[8]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B., Choud-

hary M. I., Zeinul’dina A.S. Antioxidant activity of an extract Tamarix arceuthoides Bge. // XI the International scientific conference: "a Science and education – conducting factor of strategy of Kazakhstan – 2030". – Karaganda, June 24-25, 2008 (In Rus.). [9]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B., Choudhary M. I., Tritarpenoids from Reaumuria soongаrica (Pall). Maxim. // XI the International scientific conference: " a Science and education – conducting factor of strategy " of Kazakhstan – 2030 ". – Karaganda, June 24-25, 2008 (In Rus.). [10]. Mynbayeva Zh. T., Abilov Zh. A., Rakhmadieva S. B., Choudhary M. I., Triterpens of a vegetative origin from Tamarix arceuthoides bge // XI the International scientific conference: " a Science and education – conducting factor of strategy " of Kazakhstan – 2030 ". – Karaganda, June 24-25, 2008. (In Rus.). 2010 year [1]. Bina Shaheen Siddiqui, Kalamkas Zhanarbekovna Butabayeva, Gauhar Shahmanovna Burasheva, Sobiya Perwaiz, Syed Kashif Alia and Huma Aslam Bhatti A new lignane and a new sesquiterpene from Eurotia ceratoides (L.), Tetrahedron, 2010.- 66.-1716-1720.

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Patents [1]. Karzhaubekova Zh.Zh., Siddiqui B.S., Sultanova N.A., Burasheva G.Sh. The manner of obtaining remedy possesing antibacterial activity kalidium folitinum // # 19981, Bulletin # 9 15.09.2008. [2]. Sultanova N.A., Makhmoor T., Omurkamzinova V.B., Choudhary I.M., Atta-ur-Rahman, Abilov Zh.A. Sum fraction polyphenols of Tamarix ramosissima (Tamaricaceae) posses antifungal activity // # 11936, Bulletin # 9 from 16.09.2002 (Kazakhstan). [3]. Sultanova N.A., Makhmoor T., Omurkamzinova V.B., Choudhary I.M., Atta-ur-Rahman, Abilov Zh. A. Sum fraction polyphenols of Tamarix ramosissima (Tamaricaceae) posses antibacterial activity. // # 11936, Bulletin # 9 from 16.09.2002 (Kazakhstan). [4]. Umbetova A.K., Choudhary M. I.., Burasheva G.Sh., Abilov Zh.A., Sultanova N.A. The manner of obtaining remedy posses antibacterial activity // #18431, Bulletin # 5 from 15.05.2007 (Kazakhstan) [5]. Umbetova A.K., Choudhary M. I., Burasheva G.Sh., Abilov Zh.A., Sultanova N.A. The manner obtaining of antioxidant polyphenols complexes from Tamarix laxa // #18430, Bulletin # 5 from 15.05.2007 (Kazakhstan). [6]. Yeskalieva B. K., Choudhary M. I., Burasheva G.Sh., Sultanova N.A., Abilov Zh.A. The manner of obtaining remedy posses antibacterial activity//# 19396, Bulletin # 5 from 15.05.2008(Kazakhstan) [7]. Yeskalieva B.K., Choudhary I. M., Burasheva G.Sh., Sultanova N.A., Abilov Zh.A. The manner of obtaining remedy posses antifungal //# 19792, Bulletin # 8 from 15.05.2008 (Kazakhstan). [8]. R.A Muzichkina, Yu.A. Litvinenko, Choudhary I. M., Talat Makhmoor. The manner of obtaining polyphenol complexes posses antioxidant activity //# 15794, Bulletin # 6 from 15.06.2005 (Kazakhstan). [9]. Karzhaubekova, Zh.Zh. Siddiqui Bina S. Sultanova N.A. Burasheva G.Sh. The manner of obtaining remedy possessing antibacterial activity # 1981, Bulletin # 9 15.09. 2008.

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Future Prospects Title

Proposal:

Specific Objectives:

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Chemical and pharmacological search of new therapeutic agents from natural resources. Natural recourses offer a diversity of chemical structures and strong promise to yield the biological agents of choice. It is proposed that under Pak-Kazakh Joint Research Project Programme, the new natural resources will be investigated in collaboration of Pakistani and Kazakh scientists. Investigation of natural resources to obtain new bioactive components. – Train Pakistani and Kazakh researchers in chemical and pharmacological methodologies. – Train Pakistani and Kazakh researchers leading to human recourse development and award of Ph.D. degrees.

PAKISTAN-KAZAKHSTAN COOPERATION IN PHOTOGRAPHS

Photo 1 – Meeting of Members of National Academia Republic of Kazakhstan, Faisalabad, 1998

Photo 2 – Students of Prof. Viqar Uddin Ahmad, Karachi, 2000

Photo 3 – Rosa Ranjit, Dr. Vangi Amoor, Prof. Burasheva G.Sh, Prof. Ahsana Dar, miss Alfira, Nurgul, Karachi, 2000

Photo 4 – Foring young scientists, Karachi, 2000

Photo 5 – In international conference, Peshavar, 2001

Photo 6 – Prof. Viqar Uddin Ahmad and miss Balakyz, Karachi, 2003

Photo 7 – Ms. Seema, Almagul, Balakyz and Dr.Meli Alain, Karachi, 2005

Photo 8 – Prof. Bina Siddiqui. S and Prof. Sabira Begum with students, Karachi, 2005

Photo 9 – Meeting with Minister of Science Technology and Information Technology of Pakistan Prof. Atta-ur-Rahman, Karachi, 2006

Photo 10 – Meeting Prof. Iqbal Choudhary with first vice-rector of KazNU, Almaty, 2007

Photo 11 – Ms. Mynbaeva Zhanar, Karachi, 2007

Photo 12 – PhD Bates Kudaibergenova during experiment, Karachi, 2008

Photo 13 – Dr. Mirgul Turmuhanova with Dr. Farzana Shaheen, Karachi, 2008

Photo 14 – Prof. Bina Siddiqui. S., Miss Bytabaeva Kalamkas and students, Karachi, 2008

Photo 15 – Prof. Ahsana Dar, Miss Iminova Rizvangul and students, Karachi, 2008

Photo 16 – Prof. Iqbal M. Choudhary in Almaty, 2009

Photo 17 – Meeting with Prof. Atta-ur-Rahman and Prof. M. Iqbal Choudhary, Karachi, 2009

Photo 18 – Presentation of gold medal KazNU to Director of H.E.J. Research Institute of Chemistry Dr. Panjwani Center for Molecular Medicine and Drug Research Prof. M. Iqbal Choudhary by first Vicerector KazNU Prof. Burkitbaev M.M., Almaty, 2011

Photo 19 – Visit of Prof. M. I. Choudhary for deliver lectures under PhD program, Almaty, 2011

Photo 20 – Prof. M. I. Choudhary with kazakh students, Almaty, 2011

Photo 21 – Dr. U.S. Shabana and Ms. Bates, Karachi, 2012

Photo 22 – to be continuing……..

Zh. A. Abilov and M. Iqbal Choudhary AN EXAMPLE OF SUCCESSFUL SCIENTIFIC COLLABORATION BETWEEN PAKISTAN AND KAZAKHSTAN

IB No 6016 Signed for publishing 10.10.12. Format 70x100 1/16. Offset paper. Digital printing. Volume printer’s sheet 9,5. Edition 100. Order No.1226.Publishing house “Kazakh University” Al-Farabi Kazakh National University KazNU, 71 Al-Farabi, 050040, Almaty Printed in the printing office of the “Kazakh University” publishing house

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