Discrimination of potent inhibitors of Toxoplasma gondii enoyl-acyl carrier protein reductase by a thermal shift assay.

ABSTRACT: Many microbial pathogens rely on a type II fatty acid synthesis (FASII) pathway that is distinct from the type I pathway found in humans. Enoyl-acyl carrier protein reductase (ENR) is an essential FASII pathway enzyme and the target of a number of antimicrobial drug discovery efforts. The biocide triclosan is established as a potent inhibitor of ENR and has been the starting point for medicinal chemistry studies. We evaluated a series of triclosan analogues for their ability to inhibit the growth of Toxoplasma gondii, a pervasive human pathogen, and its ENR enzyme (TgENR). Several compounds that inhibited TgENR at low nanomolar concentrations were identified but could not be further differentiated because of the limited dynamic range of the TgENR activity assay. Thus, we adapted a thermal

SUBMITTER: Afanador GA 

PROVIDER: S-EPMC3953223 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature