Synthesis and urease inhibitory activity of 1,4-benzodioxane-based thiosemicarbazones: Biochemical and computational approach

The hyperactivity of urease enzyme is associated with clinically important complications including stomach ulcers and kidney stones. This enzyme provides a suitable environment to Helicobacter pylori at low pH in the stomach, a causative agent of peptic and ulcer gastric that may lead to cancer. Natural and synthetic small molecules were reported to inhibit urease enzyme. Within this context, a new series of 1,4-benzodioxane-based thiosemicarbazones (3a-p) were synthesized and screened in vitro against urease enzyme to elucidate their anti-urease activity. All the compounds displayed potent inhibitory potential with IC50 values ranging between 3.65 ± 2.64 to 31.9 ± 1.094 μM, under positive control of thiourea (IC50 = 20.8 ± 0.75 μM). Structural activity relationship (SAR) has revealed a variation based on substituents pattern at R group. The results of docking study suggest that these compounds thermodynamically binds via nickel atoms present in the active-site of urease. The in silico docking analysis and our experimental findings are in excellent co-relation. The pharmacokinetic behavior of all the compounds were also predicted. [Display omitted] •A new series 1,4-benzodioxane-based Thiosemicarbazones derivatives (3a-p) were synthesized.•The structures were confirmed by 1H NMR, 13C NMR, ESI-MS, and single crystal X-ray diffraction.•All compounds showed significant inhibition with IC50 values in range of 3.65–31.9 μM.•The structure-activity relationship were predicted by molecular docking.•Molecular docking studies were performed to know the binding interaction at atomic level.