A review of global initiatives to fight antibiotic resistance and recent antibiotics׳ discovery.

Data from across the world have shown an overall decline in the antibiotic pipeline and continually rising resistance to all first-line and last-resort antibiotics. The gaps in our knowledge of existing prevalence and mechanisms of antibiotic resistance (ABR) are all too well known. Several decades of antibiotic abuse in humans, animals, and agricultural practices have created health emergency situations and huge socio-economic impact.

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

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.

Evaluation of small molecule SecA inhibitors against methicillin-resistant Staphylococcus aureus.

Due to the emergence and rapid spread of drug resistance in bacteria, there is an urgent need for the development of novel antimicrobials. SecA, a key component of the general bacterial secretion system required for viability and virulence, is an attractive antimicrobial target. Earlier we reported that systematical dissection of a SecA inhibitor, Rose Bengal (RB), led to the development of novel small molecule SecA inhibitors active against Escherichia coli and Bacillus subtilis.