NON-EXPERIMENTAL SEARCH FOR MOLECULES WITH ANTITUMOR ACTIVITY AND MOLECULAR DOCKING IN THE SERIES OF PYRIDINECARBOXY ACID DERIVATIVES

Abstract

Abstract. In the work, a pre-experimental screening of pyridinecarboxylic acid derivatives was performed by the PASS program, The work identified potential molecular targets for the implementation of the antitumor effect of a new domestic compound, an analogue of pyridine LHT-13-19. Using the "Autodock 4.2" software environment, flexible receptor-directed molecular biological docking was carried out in virtual reality, which makes it possible to most accurately predict the formation of a complex between a molecular structure and a biological target in real conditions of a specific biological system. For molecular docking, three-dimensional structures of the epidermal growth factor receptor (EGFR, PDB ID: 1M17, 4KN2) from the open electronic library Protein Data Bank (USA) were used. Molecules of compounds - pyridine derivatives LHT-13-19, LHT-16-19 and LHT-17-19 were synthesized in the Department of Chemistry, All-Union Research Center for Biological Active Compounds Safety (Russia). As a result of the experiments, it was found that all the studied molecules have inhibitory activity against proto-oncogenic kinases, however, in terms of the totality of predictive characteristics, as well as the likelihood of forming an antitumor effect, LHT-17-19, which was studied in docking studies, turned out to be the most promising compound. It was shown that LHT-17-19 has a high affinity for the epidermal growth factor kinase receptor EGFR-K, exhibits an affinity for the CSF1 receptor system, superior to that of all comparators - imatinib, erlotinib and pemetrexed. Also, in the process of docking approach and subsequent docking with the active site of tyrosine kinase EGFR-K and the human folate receptor FOLR2, an additional hydrogen bond is formed inside the LHT-17-19 molecule between the hydrogen proton of the amino group and the oxygen atom of the carbonyl group with atomic distances of 2.21 Å and 2 .49 Å, respectively.