中药大血藤中酚类化学成分及其抗肿瘤活性

Phenolic compounds from Sargentodoxa cuneata (Oliv.) Rehd.et Wils.and their antitumor activities

目的阐明中药大血藤中抗癌活性成分。方法以细胞周期抑制、坏死性细胞毒活性为抗癌指标 ,采用硅胶、SephadexLH 2 0、大孔树脂HP 2 0等色谱方法 ,跟踪分离活性成分 ,利用理化性质及波谱方法鉴定了化学结构 ,用SRB法及流式细胞术评价其抗癌活性。结果与结论从大血藤茎中分离得到 7个酚酸类化合物 :3,5 O 二甲基 没食子酸 (1)、原儿茶酸 (2 )、绿原酸 (3)、N (对 羟基苯乙基 )阿魏酸酰胺 (4)、对 羟基苯乙醇 (5 )、(- ) 表儿茶素 (6 )、缩合鞣质B2 (7)。化合物 3对人慢性髓性白血病K5 6 2细胞的半数抑制浓度 (IC50 )为 97 2 μg/mL ,化合物 4在 10 0 μg/mL浓度下对K5 6 2细胞的增殖抑制率为 4 6 6 %。流式细胞术检测表明 ,化合物 7对小鼠乳腺癌tsFT2 10细胞和K5 6 2细胞均显示G2 /M期抑制作用 ,为一新的细胞周期抑制剂。除化合物 2外 ,其余 6个化合物均为首次从该属植物中分离得到。

Aim To clarify the anticancer constituents from Sargentodoxa cuneata (Oliv.)Rehd.et Wils.,a Chinese folk medicine used in the treatment of cancers.Methods The separation procedure was guided by a bioassay using tsFT210 cells.Vacuum liquid column chromatography over silica gel,column chromatography over Sephadex LH 20,and HPLC were employed for the isolation and purification of the bioactive compounds.The structures of the compounds were identified by the spectroscopic method.And the anticancer activities were assayed by the SRB method and flow cytometry.Results Seven phenolic compounds were isolated and identified as 3,5 O dimethyl gallic acid(1),protocatechuic acid(2),chlorogenic acid(3),7 (4 hydroxy 3 methoxyphenyl N [7′ (4′ hydroxyphenyl)ethyl] E 8 propenamide(4), p hydroxyphenethyl alcohol(5),(-) epicatechin(6)and procyanidin B 2[epicatechin (4 β →8) epicatechin](7).Conclusion Compounds 1,3,4,5,6 and 7 are isolated for the first time from this genus.Compound 7 inhibited the cell cycle progression of tsFT210 and K562 cells at the G 2/M phase.Compounds 3 and 4 inhibited the proliferation of K562 cells with the IC 50 value of 97 2 μg/mL for compound 3 and with the inhibition rates of 46 6% at 100 μg/mL for compound 4.