Inhibition of phospholipase Cgamma1 and cancer cell proliferation by lignans and flavans from Machilus thunbergii.
Thirteen compounds were isolated from the CH2Cl2 fraction of Machilus thunbergii as phospholipase Cgamma1 (PLCgamma1) inhibitors. These compounds were identified as nine lignans, two neolignans, and two flavans by spectroscopic analysis. Of these, 5,7-di-O-methyl-3',4'-methylenated (-)-epicatechin (12) and 5,7,3'-tri-O-methyl (-)-epicatechin (13) have not been reported previously in this plant. In addition, seven compounds, machilin A (1), (-)-sesamin (3), machilin G (5), (+)-galbacin (9), licarin A (10), (-)-acuminatin (11) and compound 12 showed dose-dependent potent inhibitory activities against PLCgamma1 in vitro with IC50 values ranging from 8.8 to 26.0 microM. These lignans, neolignans, and flavans are presented as a new class of PLCgamma1 inhibitors. The brief study of the structure activity relationship of these compounds suggested that the benzene ring with the methylene dioxy group is responsible for the expression of inhibitory activities against PLCgamma1. Moreover, it is suggested that inhibition of PLCgamma1 may be an important mechanism for an antiproliferative effect on the human cancer cells. Therefore, these inhibitors may be utilized as cancer chemotherapeutic and chemopreventive agents.
Lee
Ji Suk
JS
Research group of Pain and Neuroscience, East-West Medical Research Institute, Kyung Hee University, Seoul 130-701, Korea.
Kim
Jinwoong
J
Yu
Young Uck
YU
Kim
Young Choong
YC
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005415:Flavins / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007723:Korea; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D008752:Methylene Chloride / Q000737:chemistry; D051966:Phospholipase C gamma; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D012997:Solvents; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D005415:Flavins; D017705:Lignans; D010936:Plant Extracts; D012997:Solvents; D008752:Methylene Chloride; D010738:Type C Phospholipases; D051966:Phospholipase C gamma