Novel enoyl-ACP reductase (FabI) potential inhibitors of Escherichia coli from Chinese medicine monomers

Bioorg Med Chem Lett. 2010 Jan 1;20(1):56-9. doi: 10.1016/j.bmcl.2009.11.042. Epub 2009 Nov 14.

Abstract

By structure-based virtual screening and experimental verification, two Chinese medicine monomers, luteolin and curcumin, had been proved to be uncompetitive inhibitors of enoyl-ACP reductase from Escherichia coli (EcFabI) with the inhibition constant (K(i)) of 7.1microM and 15.0microM, respectively. In particular, curcumin had apparent antibacterial activity against E. coli, and the minimum inhibition concentration (MIC(90)) was 73.7microg/mL. Importantly, fabI-overexpressing E. coli showed reduced susceptibility to the inhibitor compared with the wild-type strains, demonstrating that its antibacterial action is mediated by the inhibition of EcFabI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology
  • Binding Sites
  • Computer Simulation
  • Curcumin / chemistry*
  • Curcumin / isolation & purification
  • Curcumin / pharmacology
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / antagonists & inhibitors*
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / metabolism
  • Escherichia coli / enzymology*
  • Escherichia coli Proteins / antagonists & inhibitors*
  • Escherichia coli Proteins / metabolism
  • Fatty Acid Synthase, Type II
  • Luteolin / chemistry*
  • Luteolin / isolation & purification
  • Luteolin / pharmacology
  • Medicine, Chinese Traditional

Substances

  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)
  • fabI protein, E coli
  • Fatty Acid Synthase, Type II
  • Curcumin
  • Luteolin