THE INTERNATIONAL SCIENTIFIC AND PRACTICE CONFERENCE “ACHIEVEMENTS AND PROSPECTS FOR THE DEVELOPMENT OF PHYTOCHEMISTRY”, DEDICATED TO THE 20TH ANNIVERSARY OF “PHYTOCHEMISTRY” INTERNATIONAL SCIENTIFIC AND PRODUCTION HOLDING

 

The International Scientific and Practice Conference “Achievements and Prospects for the Development of Phytochemistry” took place on the 10-11 of April 2015, Karaganda, Republic of Kazakhstan. It has been organized on the initiative of the Committee of Science, Ministry of Education and Science of the Republic of Kazakhstan, Ministry of Healthcare and Social Development of Republic of Kazakhstan, National Academy of Sciences, Akimat of Karaganda region anddedicated to the 20th anniversary of “Phytochemistry” international scientific and production holding”.  The Conference was attended by the Minister of Education and Science of the Republic of Kazakhstan,  Akim (Governor) of  Karaganda region, Deputy Minister of Healthcare and Social Development of the Republic of Kazakhstan, heads  of a number of research institutes and universities, leading scientists and representatives of scientific centers in the field of chemistry of plant substances, pharmacology and drug technology from Germany, USA, China, Pakistan, Czech Republic, Russian Federation, Republic of Belarus, Uzbekistan, Kyrgyz Republic, Azerbaijan and Kazakhstan - in total more than 200 participants.

On the Conference the greeting of President of Republic of Kazakhstan N.A. Nazarbaev was read out.

During the Conference, the exhibition within a campaign “Made in Kazakhstan” was organized with the participation of 10 domestic pharmaceutical enterprises which presented more than 400 drug products.

The Test Centre «National Centre of drugs inspection, medical devices and equipment» of the Ministry of Healthcare and Social Development of the Republic of Kazakhstan and “International Research and Production Holding “Phytochemistry” JSC signed memorandum of understanding and cooperation”. The main objective of the memorandum is cooperation in the field of development and research of new medicinal herbal products and standard samples for their testing, development of national pharmacopeial standards for medicinal herbal.

  165 plenary, oral and poster reports were presented and discussed at the Conference in the following fields: medicinal plants ex situ, in situ and in vitro, issues of pharmacognosy and pharmaceutical chemistry; low-molecular compounds in plants, chemical modification of molecules and their properties; pharmacological researches of plant substances and clinical trials of new phytopreparations; current issues of phytopreparation technology and introduction of quality control in pharmaceutical production.

The participants of the Conference noted a high level and the actuality of the presented reports and messages, as well as a wide range of the addressed issues. Most of the presented reports showed a significant novelty, high quality and reflected the achievements in the field of fundamental and applied researches in the chemistry of plant substances. The results obtained by authors, have been already applied in practice or can be recommended for applying.


Over the last 10 years there have been researched the pharmacological properties of 100 drugs based on the natural compounds and their derivatives which passed clinical trials and were registered at the end of 2013.  Among these ones, 38 compounds are considered to be potential drugs against oncologic diseases, 26 compounds are used as anti-infective, 19 are for the treatment of cardiovascular system and metabolic disorders, 11 are against an inflammation as well as 6 compounds for the treatment of neurology. However, in the future, new types of drugs are likely to be discovered as it happened with the discovery of five herbal drugs over the last 15 years with new pharmacophores that have passed clinical trials.

In this regard, the report of Doctor of Sciences John A. Beutler from the National Cancer Institute, USA “Development of englerings for cancer” is of interest. Quantity of kidney cancer has increased for the last ten years and patient survival at the advanced stages remains very low. Guaianoic sesquiterpene englerings isolated from plants Phyllanthus, induce necrotic death of kidney tumor cells without covering normal cells. Englerings have strong and selective cytotoxic properties against kidney cancer cells at all stages, which makes them promising as a new anti-cancer drug.

In his report Professor Ludger Wessjohann (Germany) describes a new modern approach of fast and efficient technique for determining biologically active compounds without its preliminary isolation from plant extracts using modern computing correlation and chemo-enzymatic techniques.  

Directional chemical modification of native plant substance molecules opens prospects for the new derivatives with a high and purposefully altered biological activity at a relatively low toxicity. For example, the report of Doctor of Chemical Sciences, Professor E.E. Shults (Russian Federation), describes some opportunities of the directional synthetic transformations of available plant diterpenoids – lambertianic and isopimaric acids and peucedanin furocoumarin using Cu-catalyzed reactions of 1,3-dipolar cycloaddition at the key stage. 

Widespread distribution among the natural metabolites of compounds with cyclopentane fragment with unique biological properties explains the interest of synthetic chemists of leading scientific centers in directed compound synthesis of this structure. The report of Doctor of Chemical Sciences, Professor V.V. Veselovsky  (Russian Federation), describes the results of works performed at the N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, on investigation of synthetic potential of intramolecular dipolar [3+2] cycloaddition reaction of  unsaturated sylil nitronic esters which ensures various stereoselective functionalization of cyclopentane ring.

The reports of Professors T. Macek (Czech Republic) and V.A. Khripach (Belarus Republic) present data of biological activity and use of steroid hormones. Discovered properties point at the prospectivity of the mentioned phytosterols as a base of new preparations for medicine. The special attention should be paid to their anti-cholesterol effect as well as adaptogenic, immunomodulatory, antiviral and anticancer activity.                                       

Special aspects of biosynthesis of plant sesquiterpenoids and particularly possible pathways of biosynthesis of sesquiterpene lactone arglabin have been analyzed in the report of professor S.M. Adekenov (Kazakhstan).  In addition to the above, there has been demonstrated an advantage of the enantio- and stereospecifity of biosynthesis of arglabin molecule from kauniolide in comparison with chemical synthesis which occurs forming a racemate.     

In the reports of Professor P. Drašar (Czech Republic), Doctor of Chemical Sciences, Professors N. F. Salakhutdinov (Russian Federation), Zh. A. Abilov, K. M. Murzagulova, Yu. A. Shapovalov, G. Ye. Zhusupova, A. Zh. Turmukhambetov, B. I. Tuleuov (Kazakhstan) and others there have been summarized the results of extraction of biologically active compounds from plant raw materials, demonstrated the latest achievements in contemporary organic synthesis of plant compound molecules and determined its structure and preparation of drugs on its basis.

Great progress has been achieved in the use of tissue cultures (methods in vitro) for bioscreening of natural compound samples and its derivatives. The models have been developed using isolated organs and tissue sections. A.V. Rat’kin (Russian Federation) presented in his report results of the research of hypolipidemic action of sesquiterpene γ-lactone achillin in vitro on a cell culture of rats’ hepatoma.

The report by Professor E. Kmonichkova (Czech Republic), dedicated to the study of immunomodulatory activity of natural compounds using nitric oxide as a biological marker raised high interest. 

The report of the famous scientist, pharmacologist D. A. Sychev (Russian Federation) dicated his work on the Conference to the issues of introduction of pharmacogenetic tests into clinical practice. He has developed a number of pharmacogenetic tests; however, the pace of implementation of pharmacogenetics into real clinical practice is low. In order to develop a pharmacogenetic test that forecasts the efficiency and safety of the anticancer drug "Arglabin", there are required the researches in the field of molecular biology, which are aimed to search for target molecules for this drug (pharmacodynamics) as well as molecular basis of its pharmacokinetics in a patient's body.

The latest achievements in search for leading compounds are related to a virtual screening. Improving of the computer technologies enables to search for successful compounds in the vast databases more efficiently. The Conference participants deem appropriate use of virtual docking of natural compounds and their derivatives. At the present time, Holding “Phytochemistry” is going to carry out a virtual docking of 15 derivatives of arglabin on 20 key enzymatic targets (ATP-ase inhibitors (аntitubercular); COX-1 and 2 inhibitor (аnti-inflammatory); P53-MDM2 inhibitors (anticancer); EGFR inhibitors (аnticancer); CCK2 antagonist; Factor-XA inhibitors,  etc.) to determine potential compounds – sources of new drugs. In addition, it is planned modeling the interrelations of 15 derivatives of arglabin with matrix proteins (complex “ligand-protein”) and calculation of a constant for binding ligand and protein.

While standardizing raw materials, pharmaceutical substances and complete dosage forms there are used both pharmacopoeial standard samples and universal standard samples of active pharmaceutical substances and their impurities, standard samples of plant origin as well as physical and chemical standard samples to calibrate the measuring equipment. Standard samples are a factor that has a direct effect on quality of laboratory results, which allow to control the quality of all stages of drug production according to GMP standards.  A comparative analysis of standard samples of drugs of plant origin according to the Pharmacopoeia of Europe, USA and Russia is presented in the report of G.Kh. Toleuova and colleagues (Kazakhstan). In addition, results of standardization of terpenoids, flavonoids, alkaloids and ecdysteroids to develop a temporary analytical regulatory document for standard samples (cynaropicrin, menthol, artemisinin, grossheimin, achillin, glaucine) are provided. Information on analytical standard samples that are used for quality control of drug raw materials, pharmaceutical substances and complete dosage forms has been summarized. 

In the field of modern phytochemistry and nutriceuticals a significant attention is paid to creation of complex drugs containing different classes of biologically active substances by using standardized plant extracts. Producing the drugs with nanotechnology methods can improve the efficiency of active ingredients due to their selective delivery to the target organ and reduce possible side effects. Experimental data received at  the “Russian Research Center for Molecular Diagnostics and Therapy” JSC (Moscow, Russian Federation) regarding the development of docetaxel-, silybin-, vinblastine containing polymer nanocompositions  demonstrate prospectivity for new approaches for creation high-performance systems for delivery of drugs, which, in turn, reduce their toxicity and increase the treatment efficiency of socially significant diseases.

One of the promising directions of phytochemical production is the development of new technologies for phytopreparation manufacture using solid-phase mechanochemical methods presented in the reports of Yu.S. Chistyachenko and L.P. Suntsova (Russian Federation). Implementation of mechanochemical processing technique of drug raw material will enable to increase solubility of native substances.

Report of Professor Kh.I. Itzhanova (Kazakhstan) presents a production technology of original phytopreparations as tablets using modern auxiliary ingredients and equipment for film tablet coating onto oral forms.

Commercial output of substances of original drugs “Allapinin”, “Aklezin”, “Axaritmin”, “Lycorine hydrochloride”, “Galantamine hydrobromide”, “Aconitine” with output of 80-85 % of content in the plant raw materials has been organized at the Institute of Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan. Within the framework of new technology “Lipid concentrate” is produced from residuals of “Allapinin” and “Acsaritmin” drugs, which is used as a biologically active additive into the household chemistry products (report of Doctor of Technical Sciences, Professor Sh.Sh. Sagdullayev, Uzbekistan).

Professor V.F. Korsun (Russian Federation) points out in his report that today phytotherapy is an integral part of the modern clinical medicine of all countries of the modern world. It is suggested to include implementation of phytotherapy into the standards (protocols) for administering medical aid and to limit the time for processing the applications for new phytopreparations up to 1 year in the Pharmacological Committee of Ministry of Healthcare and Social Development of the Russian Federation. Also it was suggested to prepare and consider the state program of development of the phytopharmacology as one of the primary problem of population health.          

The Conference participants specifically noted the main achievements over 20 years of the International Research and Production Holding “Phytochemistry”. Within 1997-2015 more than 500 plant species growing in Kazakhstan have been investigated. It has been established that 362 plant species are promising in terms of search for new biologically active compounds; more than 1000 natural compounds have been isolated and identified, on their basis over 2000 new derivatives have been synthesized which are categorized as terpenoids, flavonoids, steroids and alkaloids, some of which showed significant antimicrobial, antiviral, antifungal, antitumor, analgesic, phagocytosis-stimulating and other kinds of activities; 72 new original phytopreparations have been developed and production organized. Among these phytopreparations there  are antitumor drug “Arglabin”, hepatoprotector “Salsocollin”, antiparasitic agent “Sausalin”, hypolipidemic agent “Aterolid”, adaptogenic drug “Ecdyphyt”, etc. More than 1500 scientific papers have been published in the peer-reviewed and top-rated journals.  25 monographs have been released. More than 100 applications for inventions have been submitted,  more than 85 patents for the Republic of Kazakhstan, 10 USA patents, 3 European patents, 3 Eurasian patents, as well as patents for China, Georgia and Ukraine have been obtained.

Within 1995-2015 14 theses of doctoral and 64 Candidate’s among holding’s co-workers have been defended.

The Karaganda Pharmaceutical Plant was built and put into operation on the base of Holding, where a full technological cycle has been developed and implemented, from the production of drug raw materials, including its processing to the manufacture of complete dosage forms of phytopreparations. The Republican Database of biologically active compounds and drugs has been established.     

While the Conference took place, the participants visited laboratories of the International Research and Production Holding “Phytochemistry” and production facilities of the Karaganda Pharmaceutical Plant.

The Conference was on high scientific level, reports of contributors gave rise to active discussion and on the basis of work the appropriate decision was made.

The conference’s participants recommended to held next international research and practice conference „Achievements and Prospects for the Development of Phytochemistry” on the basis of Irkutsk A. E. Favorsky Chemistry Institute of Siberian Branch of RAS in the June of 2017.

 

From Organizing Committee of

International Research and Production Conference

«Achievements and prospects for development of Phytochemistry»

Corresponding member of NAS  RK,

Doctor of Chemistry, Professor                                                        G. A. Atazhanova

Karaganda city, Republic of Kazakhstan