In-silico Molecular Docking and ADME/Pharmacokinetic Prediction Studies of Some Novel Benzothiazole Derivatives as Anticancer Agents for the Treatment of Breast Cancer

Abstract

Molecular docking simulation of 3 molecules of N-(1H-benzo[d]imidazol-2-yl)-7-chloro-6-fluorobenzo[d]thiazol2-amine with the target receptor aromatase was carried out so as to evaluate their theoretical binding affinities. The chemical structure of the molecules was accurately drawn using ChemDraw Ultra software, then optimized at density functional theory (DFT) using Becke’s three-parameter Lee–Yang–Parr hybrid functional (B3LYP/6-311**) basis set in a vacuum of Spartan 14 software. Subsequently, the docking operation was carried out using PyRx virtual screening software. Three compounds were developed by fusion of a benzothiazole and benzimidazole ring system targeting the treatment of breast cancer. The marketed drug Exemestane which is also an aromatase inhibitor was used as a reference molecule for docking. The highest docking score from all three molecules was -8.6 kcal/mol which is very near to the standard drug score -9.5 kcal/mol which suggests that the compound exhibited favorable protein–ligand interactions, indicating its potential as a lead candidate for further investigation. In-silico ADME and drug-likeness prediction of the molecules showed good pharmacokinetic properties having high gastrointestinal absorption, orally bioavailable, and less toxic. The outcome of the present research strengthens the relevance of these compounds as promising lead candidates for the treatment of breast cancer which could help the medicinal chemists and pharmaceutical professionals in further designing and synthesis of more potent drug candidates. Moreover, the research also encouraged the in vivo and in vitro evaluation study for the proposed designed compounds to validate the computational findings.