Synthesis, antibacterial activity evaluation and molecular docking studies of coumarin modified thiouracil derivatives as SecA inhibitor

A series of thiouracil derivatives containing coumarin were designed and synthesized with SecA inhibitor 1 as the lead. The in vitro antibacterial activities of the newly synthesized compounds were evaluated, and the results revealed that some of the new compounds (such as 14k and 14q) had strong inhibitory effect against the tested bacteria. The inhibitory activities of 14k, 14 l, 14r, 14p and 14q against SecA were tested, and the IC50 of 14K was 17.6 mu g/mL which was significantly lower than that of lead compound 1. The molecular docking of the compounds 14k, 14 l, 14r, 14p and 14q with SecA were investigated and these compounds can successfully bind to SecA in the two selected pocket. Compound 14k had strong SecA inhibitory activity and antibacterial activity, which was worthy of further study. [GRAPHICS]