Methoxylation of the Stilbenes Originated from Leaves of Cajanus cajan and Their Anti-tumor Activities in vitro

Abstract:

The aim was to obtain lead compounds with anticancer activity by O-methylation of stilbene pheolic deriatives extracted from leaves of Cajanus cajan. Four derivatives, such as longistylin C, cajanonic acid A, cajanotone and cajaninstilbene acid, were treated with iodomethane and potassium carbohydrate under mild condition. The products were purified through silica gel column chromatography and their structures were identified by spectroscopic analysis as 2-isoprenyl-3,5-dimethoxy-stilbene (1), O-methyl-cajanonic acid A (2), 5-O-methyl cajanotone (3) and 3-O-methyl cajaninstilbene acid (4), respectively. Among them, compound 3 was a new compound. Effects of 1-4 and their reactants, together with resveratrol, 4'-O-methyl resveratrol and 3,4',5-O-trimethyl resveratrol using as positive controls, on the proliferation of the cell lines of human breast cancer (MDA-MB-231), cervical cancer (HeLa), liver cancer (HepG2), colon cancer (SW480), and non-small cell lung cancer (A549, NCI-H460 and NCI-H1299) were determined by CCK-8 assay. The results showed that longistilin C distinctly inhibited the proliferation of all the seven cell lines, with the half inhibitory concentrations (IC₅₀) to MDA-MB-231, HeLa, HepG2, and SW480 at 14.4, 16.1, 19.6, and 17.4 μmol L^-1 (strong suppresion), with IC₅₀ values of 25.7-29.6 μmol L^-1 to other three cell lines of non-small cell lung cancer; cajaninstilbene acid had a weak inhibition to HepG2, A549, NCI-H460, NCI-H1299 and MDA-MB-231 cells with IC₅₀ as 44.9-78.3 μmol L^-1; tri-O-methylated resveratrol showed significantly cytotoxity against MDA-MB-231, HeLa, SW480 and HepG2 cells with IC₅₀ of 16.1-17.4 μmol L^-1; O-methylated stilbenes 1-4 did not exhibited obvious cytotoxicity in the cell lines aboved.