Synthesis and structure–activity relationship studies of N-terminal analogues of the lipopeptide antibiotics brevicidine and laterocidine. Issue 12 (8th November 2022)

• Record Type: Journal Article
• Authors: Ballantine, Ross D.; Al Ayed, Karol; Bann, Samantha J.; Hoekstra, Michael; Martin, Nathaniel I.; Cochrane, Stephen A.
• Is Part Of: RSC medicinal chemistry. Volume 13:Issue 12(2022)
• Page Start: 1640
• Page End: 1643
• Publication Date: 2022-11-08
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1039/d2md00281g
• Languages: English
• ISSNs: 2632-8682

Abstract

Abstract : SAR studies on brevicidine and laterocidine yield new analogues with strong activity against multidrug-resistant Gram-negative bacteria. Abstract : The brevicidine and laterocidine family of lipopeptide antibiotics exhibit strong activity against multidrug-resistant Gram-negative bacteria, while showing low propensity to induce resistance. Both peptides feature a branched lipid tail on the N-terminal residue, which for brevicidine is chiral. Here, we report the synthesis and biological evaluation of a library of brevicidine and laterocidine analogues wherein the N-terminal lipid is replaced with linear achiral fatty acids. Optimal lipid chain lengths were determined and new analogues with strong activity against colistin-resistant E. coli produced.