MOLECULAR DOCKING STUDIES OF NOVEL 1,2,4-TRIAZOLE DERIVATIVES WITH 5BK8 AND 9EHA PROTEIN TARGETS
Abstract
During the study, molecular docking investigations were carried out to theoretically evaluate the interactions of the synthesized compounds, N-(4-(6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phenyl)acetamide, N-(4-(6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phenyl)propionamide, and N-(4-(6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phenyl)benzamide, with biological targets. Macromolecules with the identifiers 5BK8 and 9EHA, obtained from the Protein Data Bank, were selected as biological targets for the molecular docking studies. According to the molecular docking results, the binding energies of N-(4-(6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phenyl)acetamide with the 5BK8 and 9EHA macromolecules were −8.7 and −8.0 kcal/mol, respectively. For N-(4-(6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phenyl)propionamide, the corresponding binding energies were −8.4 and −7.6 kcal/mol, whereas for N-(4-(6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phenyl)benzamide, they were −10.4 and −8.1 kcal/mol, respectively. Among the obtained results, the benzamide derivative exhibited the highest affinity toward the 5BK8 macromolecule, with a binding energy of −10.4 kcal/mol. Analysis of the interactions between the ligands and the active site of the protein revealed the formation of various non-covalent interactions involving amino acid residues, including hydrogen bonds, р-anion, р-alkyl, and van der Waals interactions. In particular, the amino acid residues ARG220, ASN217, GLU315, ASP489, LYS492, and MET496 located in the active site of the 5BK8 macromolecule were found to participate in the formation and stabilization of the ligand–protein complexes.
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