Mechanistic Duality of Bacterial Efflux Substrates and Inhibitors: Example of Simple Substituted Cinnamoyl and Naphthyl Amides.

ABSTRACT: Antibiotic resistance poses an immediate and growing threat to human health. Multidrug efflux pumps are promising targets for overcoming antibiotic resistance with small-molecule therapeutics. Previously, we identified a diaminoquinoline acrylamide, NSC-33353, as a potent inhibitor of the AcrAB-TolC efflux pump in Escherichia coli. This inhibitor potentiates the antibacterial activities of novobiocin and erythromycin upon binding to the membrane fusion protein AcrA. It is also a substrate for efflux and lacks appreciable intrinsic antibacterial activity of its own in wild-type cells. Here, we have modified the substituents of the cinnamoyl group of NSC-33353, giving rise to analogs that retain the ability to inhibit efflux, lost the features of the efflux substrates, and gained anti

SUBMITTER: D'Cunha N 

PROVIDER: S-EPMC8668026 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature