MOLECULAR DOCKING AND COMPUTATIONAL PHARMACOKINETIC STUDY OF SOME NOVEL COUMARIN–BENZOTHIAZOLE SCHIFF’S BASE FOR ANTIMICROBIAL ACTIVITY

Abstract

Objective: The present study discusses molecular docking of some novel coumarin–benzothiazole Schiff bases and the prediction of pharmacokinetic properties of potent molecules by the computational method. Methods: Five protein targets were selected for the study and their structures were taken from RCSB Protein Data Bank in PDB format. Preparation of proteins was done using Discovery Studio 2021 Client. A total of twenty derivatives were drawn using ChemDraw 20.0 and saved in Mol format. Molecular docking was performed using PyRx software. Docking results were visualized by Discovery Studio 2021 Client. The pharmacokinetic properties of the best compounds were determined using the pkCSM tool. Results: All twenty derivatives were docked against the five proteins, namely DNA Ligase (PDB ID: 3PN1), Topoisomerase (PDB ID: 3TTZ), Sterol demethylase (PDB ID: 5FSA), Enoyl-acyl-carrier protein (PDB ID: 1BVR) and Glutamate racemase (PDB ID: 5HJ7). The compound JJB18 has shown the best binding score against DNA ligase (-10.7 kcal/mol), Glutamate racemase (-8.4 kcal/mol), and Enoyl-acyl-carrier protein (-10.8 kcal/mol). Further, compound JJB19 has shown the best score for fungal sterol demethylase (-10.6 kcal/mol) and compound JJB20 towards topoisomerase (-9.4 kcal/mol) than the standard drugs. The physicochemical properties of potent derivatives were also reported. Conclusion: Molecular Docking study indicates that coumarin–benzothiazole Schiff bases may be effective inhibitors for the different microbial proteins. Additionally, in silico ADMET studies predicts drug-like features. Hence, these compounds may be considered lead molecules and further investigation of their analogues may help in the development of novel drugs for the treatment of microbial diseases.