New β-phospholactam as a carbapenem transition state analog: synthesis of a broad-spectrum inhibitor of metallo-β-lactamases

…, SK Yang, M Aitha, AE LaCuran, P Oelschlaeger…

Index: Yang, Ke-Wu; Feng, Lei; Yang, Shao-Kang; Aitha, Mahesh; Lacuran, Alecander E.; Oelschlaeger, Peter; Crowder, Michael W. Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 21 p. 5855 - 5859

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Citation Number: 9

Abstract

Abstract In an effort to test whether a transition state analog is an inhibitor of the metallo-β- lactamases, a phospholactam analog of carbapenem has been synthesized and characterized. The phospholactam 1 proved to be a weak, time-dependent inhibitor of IMP-1 (70%), CcrA (70%), L1 (70%), NDM-1 (53%), and Bla2 (94%) at an inhibitor concentration of 100 μM. The phospholactam 1 activated ImiS and BcII at the same concentration. Docking ...