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

被引：43

作者：

Saturnino, Carmela ^{[2
]}

Petrosino, Stefania ^{[1
,2
]}

Ligresti, Alessia ^{[1
]}

Palladino, Chiara ^{[2
]}

De Martino, Giovanni ^{[2
]}

Bisogno, Tiziana ^{[1
]}

Di Marzo, Vincenzo ^{[1
]}

机构：

[1] CNR, Inst Biomol Chem, Endocannabinoid Res Grp, I-80078 Pozzuoli, NA, Italy

[2] Univ Salerno, Dept Pharmaceut Sci, I-84084 Fisciano, SA, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 03期

关键词：

N-Acylethanolamines; Palmitoylethanolamide; Inflammation; Degradation; Enzyme; Endocannabinoid; Vanilloid; NAAA; MOLECULAR CHARACTERIZATION; ACUTE-INFLAMMATION; PALMITOYLETHANOLAMIDE; ANANDAMIDE; HYDROLASE; RECEPTOR; PAIN; BIOSYNTHESIS; INVOLVEMENT; ESTERS;

D O I：

10.1016/j.bmcl.2009.11.134

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 (IC50 = 10.0 mu M), without inhibiting FAAH up to 50 mu M. Compound 13 may become a useful template to design new NAAA inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1210 / 1213

页数：4

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