树豆叶二苯乙烯类成分的甲醚化和体外抗肿瘤活性

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

摘要:

为获得具有抗肿瘤活性的甲醚化先导化合物，对树豆（Cajanus cajan）叶中的二苯乙烯类成分进行甲醚化，并测定其对人肿瘤细胞的细胞毒性。将木豆素C、树豆酮酸A、Cajanotone和木豆素与碘甲烷-碳酸钾反应制备O-甲基产物，通过波谱数据分析产物结构分别鉴定为：2-异戊烯基-3，5-二甲氧基二苯乙烯（1）、树豆酮酸A甲醚（2）、5-O-methyl cajanotone（3）和3-O-甲基木豆素（4），其中化合物3是新化合物。肿瘤细胞增殖抑制实验（CCK-8法）结果表明，木豆素C对乳腺癌MDA-MB-231、宫颈癌HeLa、肝癌HepG2、结肠癌SW480及3种非小细胞肺癌细胞（A549，NCI-H460和NCI-H1299）的半数抑制浓度IC₅₀分别为14.4、16.1、19.6、17.4和25.7~29.6μmol L^-1；木豆素对宫颈癌和结肠癌之外的5种肿瘤细胞有弱抑制作用，IC₅₀为44.9~78.3μmol L^-1；而对照的3，4'，5-三甲氧基二苯乙烯（三-O-甲基白藜芦醇）对乳腺癌MDA-MB-231、宫颈癌HeLa、结肠癌SW480和肝癌HepG2细胞有较强抑制作用（IC₅₀为3.0~14.5μmol L^-1）。树豆叶二苯乙烯甲醚化衍生物1~4对7种肿瘤细胞系无明显细胞毒活性。

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.