从荜茇和黑胡椒果实中分离得到的酰胺类化合物对二酰甘油酰基转移酶的抑制作用。

Inhibition of diacylglycerol acyltransferase by alkamides isolated from the fruits of Piper longum and Piper nigrum.

作者信息

Lee Seung Woong, Rho Mun-Chual, Park Hye Ran, Choi Jung-Ho, Kang Ji Yun, Lee Jung Won, Kim Koanhoi, Lee Hyun Sun, Kim Young Kook

机构信息

Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Korea, and School of Medicine, Pusan National University, Pusan, Korea.

出版信息

J Agric Food Chem. 2006 Dec 27;54(26):9759-63. doi: 10.1021/jf061402e.

DOI:10.1021/jf061402e

PMID:17177498

Abstract

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.

摘要

抑制酰基辅酶A：二酰基甘油酰基转移酶（DGAT，EC 2.3.1.20）的药理作用已成为治疗肥胖症和2型糖尿病的一种潜在疗法。利用体外DGAT抑制试验，对长蒌叶胡椒和黑胡椒（胡椒科）果实的氯仿提取物进行生物测定导向分离，得到一种名为(2E,4Z,8E)-N-[9-(3,4-亚甲二氧基苯基)-2,4,8-壬三烯酰基]哌啶（2）的新酰胺，以及四种已知酰胺：反式断裂酰胺C（1）、胡椒壬碱（3）、胡椒罗林B（4）和脱氢胡椒壬碱（5）。化合物2 - 5对DGAT的抑制作用的IC50值分别为29.8（2）、37.2（3）、20.1（4）和21.2（5）微摩尔，但1的IC50值超过900微摩尔。这一发现表明，具有哌啶基团的化合物（2 - 5）可能是潜在的DGAT抑制剂。