From Bones to Bugs: Structure-Based Development of Raloxifene-Derived Pathoblockers That Inhibit Pyocyanin Production in <i>Pseudomonas aeruginosa</i>.

ABSTRACT: The human pathogen Pseudomonas aeruginosa is particularly notorious for its multiple resistance mechanisms. A new concept for anti-infectives is the "pathoblocker" approach, which targets virulence factors to disarm rather than kill pathogens and thus attenuates the development of resistance. Based on the estrogen receptor modulator raloxifene, which had previously been identified as a potential biosynthesis inhibitor of the virulence factor pyocyanin via in silico screening, analogues have been developed as pathoblockers against P. aeruginosa. These compounds reduce the production of pyocyanin by binding to the phenazine biosynthesis enzyme PhzB. Structure-activity relationships (SAR) were explored using nano differential scanning fluorimetry, isothermal titration cal

SUBMITTER: Thiemann M 

PROVIDER: S-EPMC11998002 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature