Molecular Docking of Potential Targets of Promising Domestic Anticancer Compound LHT-13-19

Abstract

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. The ligands were prepared using the MGL Tools 1.5.6 software environment, and their optimization was performed using the Avogadro software (USA). The molecule of the compound, an analogue of pyridine nucleoside, was synthesized in the Department of Chemistry, Technology of Synthetic Medicines and Analytical Control of All-Union Research Center for Biological Active Compounds Safety (Russia). As a result of the experiments, it was found that the LHT-13-19 molecule forms a conformational intermolecular interaction with the active centers 1M17, 4KN2 of the epidemic growth factor EGFR. The affinity is based on the formation of hydrogen and electron-acceptor bonds, characterized by high values of the scoring function and free energy value. Moreover, in terms of the strength of the affinity, the LHT-13-19 substance is not inferior to the reference molecule erlotinib.