Design, synthesis, biological evaluation and in silico study of some benzoylthioureido based hydroxamic acid derivatives and their analogues

The present investigation reports the design, synthesis and structure elucidation via elemental analyses and spectral techniques of six benzoylthioureido derivatives 6a, 6b,7a,7b, 8 and 13. Compounds 7a,7b, 8 and 13 were screened for their biological activity including carbonic anhydrase inhibition, anticancer, antimicrobial and antioxidant properties. The biological evaluation revealed a superior carbonic anhydrase inhibitory activity of compound 8 against hCAI (k_i = 58.60 nM) along with a moderate activity toward hCAII (k_i = 44.00 nM) compared to acetazolamide AAZ (k_i = 250.00 and 12.10 nM), respectively. The anticancer activity did not show any remarkable cytotoxicity. Antimicrobial and antioxidant activities of the newly synthesized compounds in addition to three previously reported sulfonamide-based derivatives 14a-c demonstrated that the tested compounds show a potent antibacterial activity against P. aeruginosa (MIC = 125–250 μg/mL) except 14a, moreover, 7a, 8 and 13 displayed a potent antifungal activity (MIC = 125 μg/mL) against C. albicans. Furthermore, compound 14b revealed a potent antioxidant activity in ABTS and DPPH assays. A molecular docking study was performed to correlate hCAI and hCAII inhibition of compound 8 with its binding pattern in the active site of the enzyme. Additionally, ADMET prediction of the synthesized compounds showed favorable physicochemical characteristics.