Design, synthesis, in vitro evaluation, molecular docking and ADME properties studies of hybrid bis-coumarin with thiadiazole as a new inhibitor of Urease.

ABSTRACT

Hybrid bis-coumarin derivatives 1-18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC50 = 21.40 ±â€¯0.21 µM). Among these derivatives, compounds 7 (IC50 = 0.29 ±â€¯0.01), 9 (IC50 = 2.4 ±â€¯0.05), 10 (IC50 = 2.25 ±â€¯0.05) and 16 (IC50 = 0.12 ±â€¯0.01) are better inhibitors of the urease compared with thiourea (IC50 = 21.40 ±â€¯0.21 µM). To find structure-activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic.