Хлебников Андрей Иванович
Доктор химических наук

Научно-образовательный центр Н.М.Кижнера, Профессор
Научно-образовательный центр Н.М.Кижнера, Ведущий научный сотрудник

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Contributions to Science

  1. Synthesis and investigation of N-ethenylhetarenes was performed. Enamines containing 9-carbazolyl, 10-phenothiazinyl, and 10-phenoxazinyl substituents conjugated with the double bond were synthesized. Their physico-chemical properties were determined by kinetic, spectroscopic, and computational methods. Hydrolysis, polymerization, dihalocarbene cycloaddition to the double bond were studied. It was shown that N ethenylhetarenes and their derivatives can be used as biologically active compounds or as monomers for the synthesis of photosensitive polymeric materials. I served as the primary investigator or co-investigator in all of these studies.

  2. Development of 3D-QSAR approach (the frontal polygon method) based on the determining local 3D-similarity of molecules. An original algorithm and computer program were developed and applied to numerous series of biologically active compounds. The method allows to perform a QSAR study among diverse and conformationally flexible compounds. The approach was successfully used for Baker triazines (dihydrofolate reductase inhibitors), urea derivatives (Cytochrome P450 inducers), azoles with anticarcinogenic activity. De novo drug design based on this methodology led to glycolurils which are highly active inducers of Cytochrome P450. I served as the primary investigator or co-investigator in all of these studies.

  3. Synthesis and investigation of transition metal complexes with nitrogen-containing heterocycles as ligands was undertaken. Complexes of substituted benzotriazole and pyrazole with Cu(II), Co(II), Hg(II) and other transition metal ions are under investigation. Biologically important ligands were synthesized and involved in reactions with metal salts. Synthetic methods for obtaining polymeric chelating ligands and corresponding macromolecular complexes have been developed. The products are being investigated in metal extraction processes, for creation of nano devices, sensors, catalysts, etc. Technique used: physico-chemical analysis by the methods of TGA, NMR, EPR, electronic spectroscopy, chromato-mass spectrometry, voltammetric measurements. Antioxidant properties were discovered for a number of copper(II) complexes containing pyrazole ligands. I served as the primary investigator or co-investigator in all of these studies.

  4. Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCR) that play an important role in leukocyte activation and chemotaxis. It has been proposed that FPRs act as sensors of pathogen-derived products that recruit leukocytes to sites of infection, where these cells exert antibacterial effector functions and clear cell debris. There is evidence that bioactive ligands acting as FPR agonists might serve as useful therapeutics in host defense and as immunomodulatory activators to enhance selective innate immune responses in order to reduce detrimental effects associated with inflammation, infectious diseases, and cancer.
    We screened small molecule libraries and utilized structure-activity relationship analysis to identify a large number of novel small-molecule FPR agonists. These compounds represent novel probes to investigate FPR function, ligand specificity, and functional responses. They also represent lead compounds for therapeutic development. I served as the primary investigator or co-investigator in all of these studies.

  5. Inflammation plays a key role in chronic inflammatory diseases, and our research group has been interested in identifying small molecules with immunomodulatory activity. We have identified a number of small molecule modulators of signaling pathways involved in inflammation. Among these compounds is one of the c-Jun N-terminal kinase inhibitors that we are currently developing in this proposal as a novel treatment for rheumatoid arthritis. Addition agonists and antagonists of chemokine receptors including CXCR2 and FPR1 were also found to exhibit immunomodulatory activity. I served as the primary investigator or co-investigator in all of these studies.

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