Laboratory of Physiologically Active Compounds (LPhAC)

Research areas:

The major scientific trends

 

• Development of new leading compounds in the most popular therapeutic areas – oncology, cardiovascular diseases, neurodegenerative diseases, analgesics, and infectious disease.
• Reactivity study of monoterpenoids in the presence of heterogeneous catalysts. Development of effective methods of catalytic conversions of organic compounds in supercritical fluids.
• Development of methods for the stereoselective synthesis, including new catalytically asymmetric systems.
• Directed chemical modification of metabolites of plant and animal origin in order to obtain new semisynthetic derivatives of valuable biological properties.
• The study of Siberian and Altai plants as a scientific basis for the development of Russian medical and preventive medications.

 

Main scientific results

 

• A new promising agent for the treatment of Parkinson's disease, who is at the stage of pre-clinical trials, was developed. Based on polysulfur compounds, an agent having high antidepressant activity, superior to that of some commercial products, was created. Compounds perspective for the development of a new structural type of analgesics, anticonvulsants were found.
• As a result of the reactivity study of the usnic acid which is a metabolite of a number of lichens, new highly active anti-TB and anti-influenza agents have been developed.
• New catalytic systems for the asymmetric oxidation of sulfides to sulfoxides and asymmetric chiral addition of diethylzink to aldehydes were created. Patent collision-free methods of asymmetric synthesis of the modern anti-ulcer drug "Esomeprazole" with the use of original catalytic systems were developed.
• As a result of phytochemical studies it was found that the roots of barberry Berberis sibirica Pall, both natural and introduced populations growing in Russia, are a practical source of isoquinoline alkaloid berberine. A technique which allows the isolation of berberine chloride with the yield up to 0.62% on the dry weight of roots was developed and patented. A review summarizing the reactions of berberine and its hydrogenated derivatives, as well as information on the biological activity of berberine and some of its derivatives was published. Methods of the direct introduction of bromine and iodine in the molecule of berberine were developed in first time.
• New semisynthetic derivative of glycyrrhetic acid, methyl soloksolon, having anticancer and anti-inflammatory activities was obtained. Its preclinical in vitro and in vivo tests have shown a high potential of this compound as a high-performance low-toxic agent in the drug development.
• Chemical transformations of stilbene glycosides, resveratroloside and pinostilbenoside  were performed and their derivatives were obtained. It was found that resveratroloside had cardioprotective properties comparable to those of resveratrol.

 

List of priority investigations

 

• Scientific basis of isolation technologies of plant metabolites of Siberian flora as a raw material source promising synthons for medicinal chemistry and pharmaceutical industries.
• Synthetic transformation of plant alkaloids, terpenoids and coumarins. The total synthesis of the substances of high pharmacological importance

 

Current projects

• RFBR Projects:
  • Creation of a basic foundation for the development of technological methods for the synthesis of physiologically active compounds from the available monoterpenoids using supercritical solvents (11-08-00171-a);
  • Creation of anti-cancer polysulfide compounds PPAR1 inhibitors (11-04-12099-ofi-m-2011);
  • The study of the fundamental laws of interaction of monoterpenoids with aromatic aldehydes to detect antiparkinsonian agents of a new structural type (11-03-00010-a);
  • Identification of the fundamental laws of the reactivity of pinane terpenoids in the presence of acidic crystalline aluminosilicate catalysts to discover new pharmacologically active compounds (10-03-00230-a);
  • The development of selective functionalization methods of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol at the methyl groups to study the effects of substituents on the antiparkinsonian activity (12-03-31257 mol_a);
  • The reactivity study of carbonyl compounds of monoterpene type in the reactions with different nitrogen-containing derivatives of adamantane to find new anxiolytic agents (12-03-31392 mol_a). Integration projects:
  • A study of genetic and neurophysiological mechanisms of actions of the brain-derived neurotrophic factor and its synthetic agonists);
  • A study of metabolites of marine and plant origin as a scientific basis for the development of important drugs;
  • Integration project of SB RAS on partner basic research No 30 (2012-2013 years) "Development of long-acting form of the neurotoxin to relieve arrhythmia on in vivo model of atrial fibrillation";
  • Search and creation of products for cancer therapy based on modified natural compounds.
• RAS and SB RAS presidium programmes:
  • The origin of life and the formation of the biosphere (Natural clays as catalysts for prebiotic reactions of chiral compounds);
  • Development of effective anticancer agents based on modified natural triterpene acids (the program "Basic Sciences for Medicine" of SB RAS);
  • Expedition project "Survey of plants of Siberia and Altai as a scientific basis for the development of domestic medicinal and preventive drugs." State contract.
  • "Preclinical studies of TB drugs based on semi-synthetic derivatives of usnic acid" (within the Federal Target Program "Development of the medical and pharmaceutical industry of the Russian Federation for the period up to 2020 and beyond"). 12411.1008799.13.002 (2012).