Diacylglycerol acyltransferase-inhibitory compounds from Erythrina senegalensis.
Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT) is proposed to be a drug target for the treatment of obesity and type 2 diabetes. Bioassay-guided fractionation of the CH(2)Cl(2)-soluble extract of the stem bark of Erythrina senegalensis, using an in vitro DGAT enzyme assay, resulted in the isolation of eight known prenylflavonoids, 8-prenylleutone (1), auriculatin (2), erysenegalensein O (3), erysenegalensein D (4), erysenegalensein N (5), derrone (6), alpinumisoflavone (7), and 6,8-diprenylgenistein (8). Compounds 1, 2-4, 6, and 8 inhibited DGAT activity, with IC(50) values ranging from 1.1 +/- 0.3 to 15.1 +/- 1.1 microg/mL. On the basis of the data obtained, we propose isoflavonoids with isoprenyl groups as a novel class of DGAT inhibitors.
Oh
Won Keun
WK
College of Pharmacy, Chosun University, Gwangju, 501-759, Korea.
Lee
Chul- Ho
C
Seo
Jee Hee
JH
Chung
Mi Yeon
MY
Cui
Long
L
Fomum
Z Tanee
ZT
Kang
Jong Seong
JS
Lee
Hyun Sun
HS
D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005591:Chemical Fractionation; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004895:Erythrina / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; C494883:Dgat1 protein, rat; D051048:Diacylglycerol O-Acyltransferase