Activation and inhibition of leukotriene A4 hydrolase aminopeptidase activity by diphenyl ether and derivatives

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6549-52. doi: 10.1016/j.bmcl.2008.10.044. Epub 2008 Oct 14.


The synthesis and biological evaluation of a series of diphenyl ether derivatives were described. The compounds can either activate or inhibit the aminopeptidase activity of leukotriene A(4) hydrolase, while at the same time do not influence the hydrolase activity. Further enzyme kinetics and molecular modeling investigation on these novel chemical activators revealed their possible activation mechanism. These compounds can be used as probes to regulate the aminopeptidase activity of leukotriene A(4) hydrolase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry, Pharmaceutical
  • Drug Design
  • Enzyme Activation
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Epoxide Hydrolases / chemistry*
  • Humans
  • Hydrolysis
  • Inhibitory Concentration 50
  • Kinetics
  • Models, Chemical
  • Models, Molecular
  • Molecular Conformation
  • Phenyl Ethers / chemistry*
  • Protein Binding
  • Substrate Specificity


  • Phenyl Ethers
  • phenyl ether
  • Epoxide Hydrolases
  • leukotriene A4 hydrolase