Synthesis of 3-alkyl enol mimics inhibitors of type II dehydroquinase: factors influencing their inhibition potency

Org Biomol Chem. 2012 May 14;10(18):3662-76. doi: 10.1039/c2ob07081b. Epub 2012 Mar 26.

Abstract

Several 3-alkylaryl mimics of the enol intermediate in the reaction catalyzed by type II dehydroquinase were synthesized to investigate the effect on the inhibition potency of replacing the oxygen atom in the side chain by a carbon atom. The length and the rigidity of the spacer was also studied. The inhibitory properties of the reported compounds against type II dehydroquinase from Mycobacterium tuberculosis and Helicobacter pylori are also reported. The binding modes of these analogs in the active site of both enzymes were studied by molecular docking using GOLD 5.0 and dynamic simulations studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enoyl-CoA Hydratase / antagonists & inhibitors*
  • Enoyl-CoA Hydratase / metabolism
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Helicobacter pylori / enzymology
  • Ketones / chemical synthesis
  • Ketones / chemistry
  • Ketones / pharmacology*
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Molecular Mimicry*
  • Molecular Structure
  • Mycobacterium tuberculosis / enzymology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Ketones
  • Enoyl-CoA Hydratase