The chemistry of natural compounds has a huge impact on the development of the main disciplines of the medical and biological profile, as well as on the solution of important practical issues in healthcare, agriculture and a number of industries. In this regard, the continued interest in research in this area is understandable.
The development of the chemistry of plant substances in Uzbekistan is associated with the activities of two scientific schools - academicians S.Yu. Yunusov and A.S. Sadykov. The foundations of research in the field of chemistry of plant substances in Uzbekistan were laid in 1935, when S.Yu. Yunusov isolated two alkaloids (remeria and armepavine) from the plant Roemeria refracta and proved their structure. In 1943, at the Institute of Chemistry (now the Institute of General and Inorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan), a laboratory of alkaloid chemistry was organized, on the basis of which in 1956, on the initiative of Academician S.Yu. Yunusov, the Institute of Plant Raw Materials and Cotton was created, renamed in 1957 at the Institute of Chemistry of Plant Substances. In 1999, the Institute was named after Academician S.Yu. Yunusov.
The structural organization of the Institute, proposed by S.Yu. Yunusov, was aimed at a comprehensive study of plant substances and the implementation of the results obtained in practice. At first, the Institute included 5 chemical laboratories: alkaloid chemistry, cotton chemistry, natural polymer chemistry, glycoside chemistry, and organic microanalysis. Then in 1956-1964. laboratories of pharmacology and chemotherapy, chemistry of lipids, medicinal and technical plants, growth substances and experimental technology were created. In 1965-1970 laboratories for the chemistry of plant proteins, physical research methods, phosphorus-containing compounds, chemistry of coumarins and flavonoids, chemistry of lactones and acids, chemistry of lignins, chemistry of carbohydrates and chemistry of nucleic acids were organized, and in 2004 - a laboratory of molecular genetics. In 1980-85 A pilot production and laboratory for the technology of synthetic drugs was created. The Institute has its own pharmacy
Currently, the Institute operates the following laboratories: chemistry of alkaloids, chemistry of glycosides, chemistry of coumarins and terpenoids, chemistry of lipids, chemistry of macromolecular compounds, physical research methods, technical and medicinal plants, technology of synthetic drugs, experimental technology, organic synthesis, pharmacology, toxicology , phytotoxicology, molecular genetics
Thus, based on its many years of experience, the Institute has developed a comprehensive “conveyor” system for phytochemical research of plants and implementation of the results obtained in practice: botanical research - chemical research - screening for biological activity - study of pharmacological and toxicological properties - development of technology for the production of substances and formulations - clinical trials - implementation into practice.
The tasks of the Institute include the chemical study of plants growing in Central Asia; establishing the structure of isolated compounds using new physicochemical research methods; implementation of the synthesis of analogues of biologically active substances; study of the structure-activity relationship; testing chemically studied compounds for biological activity; development of technology for producing bioactive substances that have demonstrated sufficiently high biological activity; organization of production of medicines based on them.
Plants produce a huge number of complex compounds that are absent in the animal body. To date, information has been accumulated on the biological activity of about 12,000 chemical compounds belonging to various classes of natural organic substances with a fully or partially established structure. Metabolism in plants leads to the accumulation of products of primary (proteins, lipids, carbohydrates, polysaccharides, nucleic acids) and secondary (alkaloids, isoprenoids, phenylpropanoids) metabolism. Any plant material contains a complex set of primary and secondary compounds, which determine the multiple nature of the action of medicinal plants.
Botanists of the Institute study the biology, phytocenoses, habitats and raw materials of the most valuable medicinal plants in Central Asia. Primary tests are being carried out to introduce plants into culture; more than 200 expeditions have been carried out to the Kyzylkum, Karakum, mountain ranges of the Tien Shan, Pamir-Alai, Dzhungar Alatau and other regions of Central Asia. The habitats and natural reserves of Ungernia Victor, Aconite white-mouthed, Psoralea drupaceae, Harmala vulgaris, Thermopsis alternate-floral, Ferula finely dissected, Ferula kuhistanica, etc. have been identified.
The Institute's staff conducted chemical studies of the products of secondary metabolism of a number of wild and cultivated plants in Central Asia.
In modern medicine, secondary metabolic products are used much more widely and more often than primary metabolites. This is due to a strong pharmacological effect and multiple effects on various systems and organs of humans and animals. INIHRV studied 292 plant species belonging to 32 families, and isolated 1250 alkaloids. The structure of 540 new alkaloids belonging to quinoline, isoquinoline, indole, pyrrolizidine, amaryllis, steroid, quinazolone, sulfur-containing, diterpene and other classes has been established. The study of the biological activity of the isolated alkaloids made it possible to identify among them. substances with antiarrhythmic, local anesthetic, antispasmodic, anti-inflammatory, gangliolytic, curare-like, sedative and other activities. It should be noted that the study of representatives of C18-diterpene alkaloids was first started at the IHRV, and their antiarrhythmic properties were first discovered here. Based on the results obtained, the drug Allapinin was created, which is produced at the Institute’s Pilot Production and sold both in Uzbekistan and abroad. The Institute's research in the field of alkaloid chemistry has found practical application in the creation of drugs such as Lycorin, Galantamine, Cytisine, Deoxypeganine, as well as more than 120 bioreagents for biomedical research.
In 1967, a laboratory of physical research methods was organized on the basis of the laboratory of organic microanalysis. Currently, this division is quite well equipped with modern physicochemical instruments and spectrometers (NMR, mass spectrometry, diffractometry, IR, UV spectroscopy, HPLC, etc.), and its qualified employees at the molecular level study primary and secondary metabolites extracted from plant sources by chemical specialists in different departments of the Institute. The laboratory is well equipped with modern computational methods for studying secondary metabolites.
The study of the chemistry of isoprenoids in Uzbekistan began at the IHRV in the late 50s. About 700 compounds were identified. Particularly noteworthy are the studies of phytoecdysteroids contained in plants of the genera Silene, Rhaponticum and Ajuga. For the first time in the world, based on phytoecdysteroids isolated from Rhaponticum cartamoides and the endemic Central Asian species Ajuga turkestanica, the drug Ecdisten with tonic and anabolic action, widely used in sports medicine, as well as the biologically active additives Austan (lacto-stimulating and immunomodulating agent) and Zhisten (used in the production of cosmetic moisturizing creams by Christian Dior). At the IHRV of the Academy of Sciences of the Republic of Uzbekistan, terpenoids from 50 species of the genus Ferula were studied and 250 compounds were isolated. It was shown for the first time that plants of this genus, in addition to terpenoid coumarins and sesquiterpene lactones, contain a new group of terpenoids characteristic of this genus - esters of terpenoid alcohols with aromatic and aliphatic acids. Based on terpenoid esters, estrogenic drugs Panoferol (for use in poultry farming) and Tefestrol (the first domestic herbal drug with estrogenic action) were created. Among the terpenoids studied at the Institute, substances with acyclo-, monocyclo-, bicyclofarnesan, germacrane, guayan, eudesmane, humulan, carotane and other types of skeleton were identified. 300 plant species of Central Asia were analyzed and the structure of 60 new lactones was established. Among them, substances with antimicrobial, insecticidal, fungicidal, antitumor, hypolipidemic, hepatoprotective and other types of biological activity were found. Based on the sesquiterpene lactone leucomysine from the plant Artemisia leucodes, Oligvon, an angioprotective and hypolipidemic drug, was created.
The Institute's staff isolated 350 glycosides. Advances in the chemistry of cardiac glycosides have made it possible to create cardiotonic drugs such as Erisimozide, Olitorizide and Strophanthindin acetate. Based on saponins, the immunostimulating drug Allochroside was created, which was used to prepare the foot-and-mouth disease vaccine.
50 plant species were subjected to a comprehensive study of coumarins, flavonoids and lignans, and over 150 substances were isolated. Among the compounds of this class, substances with pronounced hypoazotemic, hypolipidemic, antiatherosclerotic, anti-inflammatory, choleretic and antispasmodic effects were found. The drugs Cinaroside (hypoazotemic), Pinocembrin (anti-inflammatory), Psoralen and Psoberan (photosensitizing) have been developed. The antihypoxic drug Kavergal was created based on proanthocyanidins. As a result of studies conducted on the study of some secondary metabolites of cotton and plane tree leaves, more than 60 compounds were isolated, such as tocopherols, a new class of polyisoprenoids - polyprenols.
The biosynthesis of secondary metabolism products occurs on the basis of primary compounds. The intensive development of the chemistry of plant substances has led to a significant accumulation of information about the structure of chemical compounds of primary metabolism and their biological activity,
In IHRV, since 1959, lipids of 250 plant species have been characterized, the structure of 50 oxygenated acids and one halogen has been provendiacids. New types and classes of plant lipids and phosphonoanalogs of phosphatidylethanolamines have been discovered. Bioadditives used in the foam detergent Lemonchiki and Guzal have been created based on biologically active lipids.
160 plant species in Central Asia were studied for carbohydrate content. A number of polysaccharides have been identified that have plasma-replacing, antiulcer, hypocholesterolemic, emulsifying, growth-stimulating and anticoagulant properties. The bioreagent Gledol has been developed and is used to isolate immunocompetent blood cells. This drug is an analogue of the imported drug Ficoll.
An in-depth chemical study of plant proteins began at the IHRV of the Academy of Sciences of the Republic of Uzbekistan in 1966. For the first time, the primary and secondary structures of 7S and 11S globulins, cotton esterases and ricin T from castor bean seeds were determined. Methods of protein markers have been developed to determine the species of cotton, as well as an immunochemical method for assessing wilt resistance based on protease inhibitors. Based on enzymes from the milky juice of the melon tree Carica papaya, the drug Cucumazim was created, which has a broad-spectrum proteolytic activity, due to which it promotes the breakdown of proteins in necrotic tissue and is used in traumatological, surgical and gynecological practice. Since 1970, the Institute has been conducting work on the study of plant lignins. In recent years, research has been carried out with the aim of targeted modification of technical lignins, as a result, plant growth stimulants (Roslin, Nitromel), sorbents (GLRL - hydrolyzed lignin of rice husk, GLSHSH - hydrolyzed lignin of cotton seed husks, NL - nitro lignin), rust converters and other drugs.
In 1962, the Institute organized a laboratory of organic synthesis, and in 1994 - a department of organic synthesis, the task of which is to develop the theoretical foundations for the search and synthesis of new chemical plant protection products, as well as to study reaction mechanisms. In addition, the department studies plant growth regulators and analogues of known chemical plant protection products from diseases and pests, purposefully synthesizes new herbicides, fungicides, bactericides, defoliants, plant growth stimulants, and establishes the relationship between biological activity and chemical structure. The department has developed an economically convenient method for obtaining the synthetic alkaloid Deoxypeganine hydrochloride. Fungicide Olgin is approved for use in the fight against certain plant diseases. The biostimulator Uchkun has been created, which increases the yield of many agricultural crops. As a result of the work carried out on a multi-stage selection of active compounds, the defoliant Butylcaptax for fine-fiber cotton varieties, the systemic fungicide Uzgen, drugs against cotton wilt KMAX and root rot and cotton gommosis Nikamizolon were recommended in the USSR.
The development of technologies for the production of herbal and synthetic drugs is carried out by the technological laboratories of the Institute. 50 original technologies for the production of medicines, plant growth regulators and food products have been created. The main developments were implemented in Uzbekistan (Tashkhimpharmzavod, Khimprom plants in Fergana, Navoi, Kokand MZhK, etc.); in Kazakhstan (Chimkent Pharmaceutical Plant); in Russia (VILR, Manturovsky Pharmaceutical Plant, etc.). Technologies for the production of such import-substituting anthelmintic drugs as Medamin, Albendazole and Phenasal have been developed. Technological schemes for the production of the drugs Lidocaine, Ridomil, Toluin and Ethoxylin have been developed. A new method for obtaining the active substance of the drug Rosalin has been developed. Technologies for the drugs Linkazol, Nikamizolon, Roslin, Tetranil, KMAX, Kuscid for agriculture have been created.
Thanks to the joint work of chemists, pharmacologists and technologists, 2000 plant substances were studied, clinical trials of 60 drugs and dietary supplements were conducted, 30 drugs were recommended for use in medical practice by the Pharmacological Committee of the USSR and the Pharmacological Committee of the Republic of Uzbekistan.
The original scientific works of chemists and pharmacologists of the Institute have received recognition at the world level, and the Institute’s products are sold not only in the Republic of Uzbekistan, but also abroad. Currently, IHRV is one of the leading centers for the study of plant substances and the creation of products based on them.
Pilot production, organized at the Institute in 1984, currently combines practically three modules: a module for the production of natural medicines, a module for the production of synthetic medicines, and a module for the production of agricultural medicines. In them, on a semi-industrial and industrial scale, work is underway to produce medicinal substances from plant sources, based on synthesis, as well as means of protecting and stimulating plant growth. Pilot production ensures the supply of substances and finished preparationsrm of medicines according to the developments of the Institute both in the Republic, and their export to foreign countries, ensuring the flow of contractual and foreign exchange funds. The Institute's pilot production facility currently produces 15 medical products and dietary supplements.
The Institute publishes the international journal “Chemistry of Natural Compounds”, which is translated into English by Springer and distributed in many countries around the world in two versions. Subscription to the magazine and its rating are growing from year to year.
