摘要/Abstract

大风子素是一类自然界稀有的黄酮木质素类化合物，因其稀有，至今对它的结构修饰和活性研究较少.以廉价易得的水飞蓟素为原料，合成了C-23位碘代的次大风子素.再经过叠氮化、还原和酰胺化，得到了15个次大风子素的酰胺类衍生物.应用三种人癌细胞对这些化合物进行了初步的抗癌活性评价，结果显示部分化合物对人非小细胞肺癌细胞（A549）具有良好的增值抑制活性，其半数抑制浓度（IC₅₀）均小于10 μmol·L^-1；23-（3，4-二甲氧基苯甲酰胺基）次大风子素（6b）和23-（2-氯-6-氟苯甲酰胺基）次大风子素（6f）对于人宫颈癌细胞（HeLa）显示出了较好的抑制活性；23-（4-氟苯甲酰胺基）次大风子素（6g）和23-[3，5-双（三氟甲基）苯甲酰胺基]次大风子素（6m）则对人乳腺癌细胞（MCF-7）具有良好的抑制活性.这些结果表明，这类化合物对正常肝细胞毒性较小，而对癌细胞增殖有一定抑制作用，值得深入研究以开发新型抗癌药物.
关键词: 次大风子素, 水飞蓟素, 结构衍生, 抗癌活性
Hydnocarpins are a rare type of flavonoligan compounds occurring in nature. Because of their rarity, only a few research has been devoted on their structural modification and activity. In this work, 23-iodo hydnocarpin D was synthesized from silibinin, which is cheap and commericially available. After azidation, reduction and amidation, 15 amido-derivatives of hydnocarpin D were obtained. These compounds with regard to their anticancer activities were evaluated on three kinds of human cancer cells, and the results showed that some compounds are active on A549 with IC₅₀ values less than 10 μmol·L^-1. 23-(3,4-Dimethoxybenzamido)hydnocarpin D (6b) and 23-(2-chloro-4-fluorobenzamido)hydnocarpin D (6f) can strongly inhibit the growth of HeLa cells. 23-(4-Fluorobenzamido)hydnocarpin D (6g) and 23-[3,5-bis(trifluoromethyl)benzamido]-hydnocarpin D (6m) showed potent activity against MCF-7 cells. These preliminary results testified that the synthsis of amido-derivative of hydnocarpin D could be an option for the development of new anti-cancer drug candidates.
Key words: hydnocarpin D, silibinin, structural modification, anticancer activity


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