Comparative study of the inhibition of metallo-beta-lactamases (IMP-1 and VIM-2) by thiol compounds that contain a hydrophobic group

Biol Pharm Bull. 2004 Jun;27(6):851-6. doi: 10.1248/bpb.27.851.


For the purpose of screening of inhibitors that are effective for wide range of metallo-beta-lactamases, the inhibitory effect of two series of compounds, 2-omega-phenylalkyl-3-mercaptopropionic acid (PhenylCnSH (n=1-4)) and N-[(7-chloro-quinolin-4-ylamino)-alkyl]-3-mercapto-propionamide (QuinolineCnSH (n=2-6)), where n denotes the alkyl chain length, on metallo-beta-lactamases IMP-1 and VIM-2 was examined. These inhibitors contain a thiol group and a hydrophobic group linked by variable-length methylene chain. PhenylCnSH (n=1-4) was found to be a potent inhibitor of both IMP-1 and VIM-2. PhenylC4SH was the potent inhibitor of both IMP-1 (IC(50)=1.2 microM) and VIM-2 (IC(50)=1.1 microM) among this study. When the number of methylene units was varied, QuinolineC4SH showed the maximum inhibitory activity against IMP-1 and VIM-2 (IC(50)=2.5 microM and IC(50)=2.4 microM). The relationship between the inhibitory effect of the alkyl chain length was different for both series of inhibitors, suggesting that IMP-1 has a tighter binding site than VIM-2. QuinolineCnSH did not serve as a fluorescence reagent for metallo-beta-lactamases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydrophobic and Hydrophilic Interactions*
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology*
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / metabolism


  • Enzyme Inhibitors
  • Sulfhydryl Compounds
  • beta-Lactamase Inhibitors
  • VIM-2 beta-lactamase
  • beta-lactamase IMP-1
  • beta-Lactamases