Developing a scaffold for urease inhibition based on benzothiazoles: Synthesis, docking analysis, and therapeutic potential
Musa Özil, Özge Tuzcuoğlu, Mustafa Emirik, Nimet Baltaş
Abstract
Abstract The synthesis, in silico molecular docking, and in vitro urease inhibition studies of a novel series of benzothiazole derivatives are reported. The title compounds in the two series, namely, 2‐({5‐[(benzothiazol‐2‐ylthio)methyl]‐1,3,4‐oxadiazol‐2‐yl}thio)‐1‐(4‐substituted‐phenyl)ethan‐1‐one and 2‐(benzothiazol‐2‐ylthio)‐1‐(4‐substituted‐phenyl)ethan‐1‐one oxime, were synthesized by the reaction of benzo[ d ]thiazole‐2‐thiol with different kinds of intermediates in several steps using both conventional and microwave techniques. All compounds were found to have an excellent degree of urease‐inhibitory potential ranging between 16.16 ± 0.54 and 105.32 ± 2.10 µM when compared with the standard inhibitor acetohydroxamic acid with IC 50 = 320.70 ± 4.24 µM. The structure–activity relationship was established in detail. The binding interactions of the compounds with the enzyme were confirmed through molecular docking. Further, 100 ‐ns molecular dynamics simulations were performed to investigate the stability and structural perturbations experienced by the most potent compound over the urease active site.