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ID: ALA1158443

Journal: Bioorg Med Chem Lett

Title: Discovery of novel lipophilic inhibitors of OXA-10 enzyme (class D beta-lactamase) by screening amino analogs and homologs of citrate and isocitrate.

Authors: Beck J, Vercheval L, Bebrone C, Herteg-Fernea A, Lassaux P, Marchand-Brynaert J.

Abstract: Aminocitrate (and homolog) derivatives have been prepared by bis-alkylation of glycinate Schiff bases with bromoacetates (and ethyl acrylate), followed by N-acylation and esters (partial or complete) deprotection. Aminoisocitrate was similarly obtained by mono-alkylation with diethyl fumarate. Evaluation against representative beta-lactamases revealed that the free acid derivatives are modest inhibitors of class A enzymes, whilst their benzyl esters showed a good inhibition of OXA-10 (class D enzyme). A docking experiment featured hydrophobic interactions in the active site.

CiteXplore: 19467869

DOI: 10.1016/j.bmcl.2009.04.149