In silico evaluation of the pharmacodynamic component of the interaction of S-alkyl derivatives of 5-methyl-4-(p-tolyl)-1,2,4-triazole-3-thiol with some biological targets

Abstract

Derivatives of 1,2,4-triazole open wide opportunities for modern and progressive scientists in the development of innovative medicines. These compounds are known for their variability and structural flexibility, which allows scientists to experiment and create new molecules with unique properties. The use of 1,2,4-triazole derivatives in the creation of drugs is based on their ability to interact with biological systems and molecular targets. These compounds can be aimed at regulating physiological processes, reducing manifestations of pathological conditions or enhancing necessary biological reactions. Directed modification of the structure of 1,2,4-triazole derivatives allows to create biologically active compounds with improved properties. The aim of the work was to study in silico and to evaluate the possible interaction of a virtual series of S-alkyl derivatives of 5-methyl-4-(p-tolyl)-1,2,4-triazole-3-thiol with some enzyme systems. Materials and methods. A computer method (molecular docking) for predicting and evaluating the interaction between a ligand molecule and a target protein structure. Ligand preparation was performed using MarvinSketch 6.3.0, Hyper Chem 8, and AutoDockTools-1.5.6 programs. Enzyme preparation involved the use of Discovery Studio 4.0 and AutoDockTools-1.5.6 software packages. Direct molecular docking was performed using the Vina program. Results. A virtual series of S-alkyl derivatives of 5-methyl-4-(p-tolyl)-1,2,4-triazole-3-thiol with the potential possibility of creating a biologically active substance has been constructed. Using the Vina software tool, the nature and number of amino acid residues of the active centers of model enzymes, with which the proposed ligands coordinate and bind, were determined. According to the results of docking studies, the predicted affinity for lanosterol-14α-demethylase was determined. The effect on the receptor tyrosine kinase of anaplastic lymphoma is somewhat inferior in terms of qualitative and quantitative indicators. Conclusions. Using the method of molecular docking, it was established that S-alkyl derivatives of 5-methyl-4-(p-tolyl)-1,2,4-triazole-3-thiol have a fairly significant potential for the manifestation of antifungal activity, which justifies the further synthesis of these compounds and more in-depth study of fungistatic and fungicidal properties. Docking results for anaplastic lymphoma kinase show little promise in the development of anticancer agents.