Inhibition of diacylglycerol acyltransferase by alkamides isolated from the fruits of Piper longum and Piper nigrum.
Pharmacological inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) has emerged as a potential therapy for the treatment of obesity and type 2 diabetes. Bioassay-guided isolation of CHCl3 extracts of the fruits of Piper longum and Piper nigum (Piperaceae), using an in vitro DGAT inhibitory assay, lead to isolation of a new alkamide named (2E,4Z,8E)-N-[9-(3,4-methylenedioxyphenyl)-2,4,8-nonatrienoyl]piperidine (2), together with four known alkamides: retrofractamide C (1), pipernonaline (3), piperrolein B (4), and dehydropipernonaline (5). Compounds 2-5 inhibited DGAT with IC50 values of 29.8 (2), 37.2 (3), 20.1 (4), and 21.2 (5) microM, respectively, but the IC50 value for 1 was more than 900 microM. This finding indicates that compounds possessing piperidine groups (2-5) can be potential DGAT inhibitors.
Lee
Seung Woong
SW
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Korea, and School of Medicine, Pusan National University, Pusan, Korea.
Rho
Mun-Chual
MC
Park
Hye Ran
HR
Choi
Jung-Ho
JH
Kang
Ji Yun
JY
Lee
Jung Won
JW
Kim
Koanhoi
K
Lee
Hyun Sun
HS
Kim
Young Kook
YK
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology; D000577:Amides / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009765:Obesity / Q000188:drug therapy; D031701:Piper / Q000737:chemistry*; D029222:Piper nigrum / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000470:Alkaloids; D000577:Amides; D004791:Enzyme Inhibitors; D051048:Diacylglycerol O-Acyltransferase