Burkholderia pseudomallei is the causative agent of melioidosis, a severe and often fatal infection that manifests as pneumonia or septicemia. It is a significant cause of morbidity and mortality in several countries in southeast Asia.  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. We discovered that nitroxoline displayed excellent inhibition potency in the BpMetAP1 enzyme activity assay (IC50 = 60 nM) and completely inhibits the growth of B. pseudomallei and B. thailandensis.  We have synthesized a series of nitroxoline analogs and determined their ability to inhibit BpMetAP1 and inhibit growth of B. thailandensis.  The poster will report the design, synthesis and activity of the BpMetAP1 inhibitors.

Discovery of inhibitors of <i>Burkholderia pseudomallei </i>methionine aminopeptidase with antibacterial activity

246th National Meeting (2013)

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Discovery of inhibitors of Burkholderia pseudomallei methionine aminopeptidase with antibacterial activity