Discovery of novel bacterial topoisomerase I inhibitors by use of in silico docking and in vitro assays.

ABSTRACT: Topoisomerases are important targets for antibacterial and anticancer therapies. Bacterial topoisomerase I remains to be exploited for antibiotics that can be used in the clinic. Inhibitors of bacterial topoisomerase I may provide leads for novel antibacterial drugs against pathogens resistant to current antibiotics. TB is the leading infectious cause of death worldwide, and new TB drugs against an alternative target are urgently needed to overcome multi-drug resistance. Mycobacterium tuberculosis topoisomerase I (MtbTopI) has been validated genetically and chemically as a TB drug target. Here we conducted in silico screening targeting an active site pocket of MtbTopI. The top hits were assayed for inhibition of MtbTopI activity. The shared structural motif found in the active hits was uti

SUBMITTER: Sandhaus S 

PROVIDER: S-EPMC5780498 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature