A novel, rapid and eco-sustainable approach for the synthesis of novel benzothiazole derivatives as potent urease inhibitors: biological assay, molecular docking, dynamic simulation, DFT and ADMET studies

Abstract

Recently, benzothiazole derivatives have garnered significant attention among the research community due to their pharmaceutical and biological significance. Likewise, in this study, novel benzothiazole derivatives were synthesized via a novel green approach and characterized by IR, NMR, and ESI MS spectroscopic methods. The synthesized compounds were evaluated for their urease inhibitory potential. All analogs exhibited varied degrees of urease inhibitory potential with IC50 values ranging between 6.01±0.23 and 21.07±0.77 μM, when compared with thiourea as the standard urease inhibitor (IC50= 11.58±0.34 μM). Among the tested derivatives, compound 3b (6.01±0.23 μM) was identified as the most potent inhibitor of urease. Based on the promising in vitro evaluation, a further in-silico study was carried out in order to understand the structure-activity relationship using DFT calculation. Molecular docking and ADMET prediction were investigated to evaluate the affinity of our synthesized compounds with anti-ureas targets. Then, a molecular dynamic simulation was suggested to confirm the stability of our derivatives in interaction within the active site.