Olefinic side chain modification of fusidic acid enhances anti-MRSA activity and mitigates resistance development.

ABSTRACT: The escalating prevalence of antibiotic resistance underscores the urgent need for innovative antimicrobial agents. Fusidic acid (FA), a fungal-derived tetracyclic triterpene clinically employed against methicillin-resistant Staphylococcus aureus (MRSA), is limited by rapid resistance development and elevated MIC values in resistant strains. While previous olefinic side chain (Δ^24,25) modifications yielded FA derivatives with retained anti-MRSA activity, most analogs exhibited compromised efficacy against Gram-positive bacteria. To address this limitation, we systematically engineered the olefinic side chain through Wittig and olefin metathesis reactions, synthesizing 26 novel FA derivatives. Compound 10a emerged as a standout candidate, demonstrating MIC value lower than

SUBMITTER: Wu WH 

PROVIDER: S-EPMC12435587 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature