Identification of a Series Containing a Pentafluorophenyl Moiety That Targets Pks13 to Inhibit Growth of <i>Mycobacterium tuberculosis</i>.

ABSTRACT: Although not currently in the infectious disease spotlight, there is still a pressing need for new agents to treat tuberculosis caused by Mycobacterium tuberculosis. As there is an ever-increasing amount of clinical resistance to the current drugs, ideally new drugs would be found against novel targets to circumvent pre-existing resistance. A phenotypic growth screen identified a novel singleton, 1, as an inhibitor of M. tuberculosis growth. Mechanism-of-action studies determined that 1 targeted Pks13, an essential enzyme in cell wall biosynthesis that, as of yet, has not been targeted by agents in the clinic. The reactive nature of the pentafluorophenyl warhead meant that the molecule was inherently metabolically unstable. A medicinal chemistry optimization pro

SUBMITTER: Green SR 

PROVIDER: S-EPMC11915372 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature