2. Academic Validation
  3. Synthesis and biological evaluation of new potential inhibitors of N-acylethanolamine hydrolyzing acid amidase

Synthesis and biological evaluation of new potential inhibitors of N-acylethanolamine hydrolyzing acid amidase

  • Bioorg Med Chem Lett. 2010 Feb 1;20(3):1210-3. doi: 10.1016/j.bmcl.2009.11.134.
Carmela Saturnino 1,  Stefania Petrosino,  Alessia Ligresti,  Chiara Palladino,  Giovanni De Martino,  Tiziana Bisogno,  Vincenzo Di Marzo
Affiliations

Affiliation

  • 1 Department of Pharmaceutical Sciences, University of Salerno, Via Ponte don Melillo 84084, Fisciano, SA, Italy.
PMID: 20022504 DOI: 10.1016/j.bmcl.2009.11.134
Abstract

N-Acylethanolamines, including N-palmitoyl-ethanolamine (PEA), are hydrolyzed to the corresponding fatty acids and ethanolamine by fatty acid amide hydrolase (FAAH). Recently, N-acylethanolamine-hydrolyzing acid amidase (NAAA) was identified as being able to specifically hydrolyze PEA. In order to find selective and effective inhibitors of this enzyme, we synthesized and screened several amides, retroamides, esters, retroesters and carbamates of palmitic acid (1-21) and esters with C15 and C17 alkyl chains (22-27). Cyclopentylhexadecanoate (13) exhibited the highest inhibitory activity on NAAA (IC(50)=10.0 microM), without inhibiting FAAH up to 50 microM. Compound 13 may become a useful template to design new NAAA inhibitors.

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