Small-Molecule Inhibitors Targeting Topoisomerase I as Novel Antituberculosis Agents.

ABSTRACT: Bacterial topoisomerase functions are required for regulation of DNA supercoiling and overcoming the DNA topological barriers that are encountered during many vital cellular processes. DNA gyrase and topoisomerase IV of the type IIA bacterial topoisomerase family are important clinical targets for antibacterial therapy. Topoisomerase I, belonging to the type IA topoisomerase family, has recently been validated as a potential antitubercular target. The topoisomerase I activity has been shown to be essential for bacterial viability and infection in a murine model of tuberculosis. Mixture-based combinatorial libraries were screened in this study to identify novel bacterial topoisomerase I inhibitors. Using positional-scanning deconvolution, selective small-molecule inhibitors of bacterial top

SUBMITTER: Sandhaus S 

PROVIDER: S-EPMC4914652 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature