Lipophilic amines as potent inhibitors of N-acylethanolamine-hydrolyzing acid amidase

Bioorg Med Chem. 2012 Jun 1;20(11):3658-65. doi: 10.1016/j.bmc.2012.03.065. Epub 2012 Apr 4.

Abstract

N-Acylethanolamines (NAEs) including N-arachidonoylethanolamine (anandamide) and N-palmitoylethanolamine are endogenous lipid mediators. These molecules are degraded to the corresponding fatty acids and ethanolamine by fatty acid amide hydrolase (FAAH) or NAE-hydrolyzing acid amidase (NAAA). Lipophilic amines, especially pentadecylamine (2c) and tridecyl 2-aminoacetate (11b), were found to exhibit potent NAAA inhibitory activities (IC(50)=5.7 and 11.8μM), with much weaker effects on FAAH. These simple structures would provide a scaffold for further improvement in NAAA inhibitory activity.

MeSH terms

  • Amidohydrolases / antagonists & inhibitors*
  • Amines / chemistry
  • Amines / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Inhibitory Concentration 50
  • Male
  • Molecular Structure
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • Amines
  • Enzyme Inhibitors
  • tridecyl 2-aminoacetate
  • pentadecylamine
  • Amidohydrolases
  • N-acylethanolamine amidohydrolase
  • N-acylethanolamine-hydrolyzing acid amidase, rat
  • Glycine