Armeniaspirol analogues with more potent Gram-positive antibiotic activity show enhanced inhibition of the ATP-dependent proteases ClpXP and ClpYQ.

ABSTRACT: Antibiotics with fundamentally new mechanisms of action such as the armeniaspirols, which target the ATP-dependent proteases ClpXP and ClpYQ, must be developed to combat antimicrobial resistance. While the mechanism of action of armeniaspirol against Gram-positive bacteria is understood, little is known about the structure-activity relationship for its antibiotic activity. Based on the preliminary data showing that modifications of armeniaspirol's N-methyl group increased antibiotic potency, we probed the structure-activity relationship of N-alkyl armeniaspirol derivatives. A series of focused derivatives were synthesized and evaluated for antibiotic activity against clinically relevant pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resi

SUBMITTER: Darnowski MG 

PROVIDER: S-EPMC9020616 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature