Assessment of possible biomarkers of individual representatives of 1,4-dihydropyridines by methods of molecular docking and predictor analysis

Abstract

Introduction: Some of the promising classes of chemical compounds for research are 1,4-dihydropyridines, which have potential biological activity and low toxicity. The use of modern technologies for the analysis of substances in silico makes it possible to predict their potential biological effects with a high degree of probability, thereby facilitating further preclinical studies.

Materials and Methods: For the purpose of predictive analysis and molecular docking, 6 newcompounds of the 1,4-dihydropyridine group were selected with lab codes SD1-874, F02-104, AS-143, AS-014, AS-144, AS-162. The studied compounds were subjected to predictive analysisin silico. Based on its results, the ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters were predicted. PASS Online, Molinspiration Property Calculation Serviceand OSIRIS Property Explorer services were used for predictor analysis. Molecular docking was carried out using the GalaxyWEB Sagittarius service, followed by evaluation of the results usingthe RCSB Protein Data Bank and UniProt Consortium databases. Based on the results of the calculation of physical and chemical parameters, the presence of Lipinski’s criteria was evaluatedin all the samples studied.

Results and Discussion: Of the 6 compounds under consideration, the SD1-874 sample haspotential oral activity, according to Lipinski's criteria. Based on the results of predictive analysis in silico, all the studied substances, except SD1-874, are potentially capable of blocking calcium channels. SD1-874 probably has an effect on lipid and carbohydrate metabolism. Evaluating the results of molecular docking, three groups of proteins can be distinguished with which the studied samples can potentially conjugate: a group of proteins that regulate the processes of apoptosis, mitosis, and DNA transcription, a group of proteins that affect blood clotting, and a group that affects the metabolism of lipoproteins, lipids, and glucose. The ability to conjugate with calcium channel subunits is also noted; however, the probability of such an interaction by the molecular docking program is estimated as unlikely. All the studied compounds interact withvarious isoforms of cytochrome P450.

Conclusion. According to the results of predictor analysis and the results of molecular docking, among the 6 compounds of 1,4-dihydropyridines selected for analysis, the compound with lab codes SD1-874 is considered the most promising for further study due to the presence of oral bioactivity.

Graphical Abstract