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

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

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

Bioorg Med Chem Lett. 2009 Jul 1;19(13):3593-7. doi: 10.1016/j.bmcl.2009.04.149. Epub 2009 May 6.

PubMed ID
19467869 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Citric acidBeta-lactamaseKi (nM)490000N/AN/ADetails