新型 N-酰基乙醇胺水解酸酰胺酶潜在抑制剂的合成与生物评价。
Synthesis and biological evaluation of new potential inhibitors of N-acylethanolamine hydrolyzing acid amidase.
机构信息
Department of Pharmaceutical Sciences, University of Salerno, Via Ponte don Melillo 84084, Fisciano, SA, Italy.
出版信息
Bioorg Med Chem Lett. 2010 Feb 1;20(3):1210-3. doi: 10.1016/j.bmcl.2009.11.134. Epub 2009 Dec 4.
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.
N-酰基乙醇胺，包括 N-棕榈酰乙醇胺（PEA），可被脂肪酸酰胺水解酶（FAAH）水解为相应的脂肪酸和乙醇胺。最近，N-酰基乙醇胺水解酸酰胺酶（NAAA）被鉴定为能够特异性水解 PEA。为了找到该酶的选择性和有效抑制剂，我们合成并筛选了几种棕榈酸（1-21）的酰胺、反酰胺、酯、反酯和氨基甲酸酯，以及 C15 和 C17 烷基链的酯（22-27）。环戊基十六烷酸酯（13）对 NAAA 的抑制活性最高（IC50=10.0 microM），而对 FAAH 的抑制作用直到 50 microM 时才显现。化合物 13 可能成为设计新型 NAAA 抑制剂的有用模板。
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