Design, Synthesis and Evaluation of Triazole-Pyrimidine Analogues as SecA Inhibitors.

ABSTRACT: SecA, a key component of the bacterial Sec-dependent secretion pathway, is an attractive target for the development of new antimicrobial agents. Through a combination of virtual screening and experimental exploration of the surrounding chemical space, we identified a hit bistriazole SecA inhibitor, SCA-21, and studied a series of analogues by systematic dissections of the core scaffold. Evaluation of these analogues allowed us to establish an initial structure-activity relationship in SecA inhibition. The best compounds in this group are potent inhibitors of SecA-dependent protein-conducting channel activity and protein translocation activity at low- to sub-micromolar concentrations. They also have minimal inhibitory concentration (MIC) values against various strains of bacteria that corre

SUBMITTER: Cui J 

PROVIDER: S-EPMC4778717 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature