title: Macamides and their synthetic analogs: evaluation of in vitro FAAH inhibition.
abstract: Maca (Lepidium meyenii), a traditional food crop of the Peruvian Andes is now widely touted as a dietary supplement. Among the various chemical constituents isolated from the plant are a unique series of non-polar, long-chain fatty acid N-benzylamides known as macamides. We have synthesized 11 of the 19 reported macamides and have tested each as potential inhibitors of the human enzyme, fatty acid amide hydrolase (FAAH). The five most potent macamides were FAAH inhibitors (IC50=10-17μM). These amides were derivatives of oleic, linoleic and linolenic acids and benzylamine or 3-methoxybenzylamine. Of the three compounds evaluated in a pre-incubation time study, two macamides were not irreversible inhibitors of FAAH. The third, a carbamate structurally related to macamides, was shown to be an irreversible inhibitor of FAAH (IC50=0.153μM).
authors.affiliation: MCPHS University, 179 Longwood Avenue, Boston, MA 02115, USA; ArQule, Inc., 19 Presidential Way, Woburn, MA 01801, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Kelley
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pino-Figueroa
authors.forename: Huyen D
authors.initials: HD
authors.lastname: Vu
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Maher
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D029686:Lepidium / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D004791:Enzyme Inhibitors; D000099252:Fatty Acid Amide Hydrolases
keywords: 3-Methoxybenzylamine; Anandamide; Carbamate; FAAH; Fatty acid amide; Lepidium meyenii; Maca; Macamide; OL-135; Oleamide; PF-750; Urea