Discovery of Inhibitors of <i>Burkholderia pseudomallei</i> Methionine Aminopeptidase with Antibacterial Activity

Abstract

Evaluation of a series of MetAP inhibitors in an in vitro enzyme activity assay led to the first identification of potent molecules that show significant growth inhibition against Burkholderia pseudomallei . Nitroxoline analogues show excellent inhibition potency in the BpMetAP1 enzyme activity assay with the lowest IC 50 of 30 nM and inhibit the growth of B. pseudomallei and B. thailandensis at concentrations ≥31 μM.