九节龙皂苷I衍生物的合成及细胞毒活性研究

目的对九节龙皂苷Ⅰ进行结构修饰得到新的结构类似物,并对其抗肿瘤活性进行研究。方法通过对九节龙皂苷Ⅰ的30位醛基进行氧化、还原或氨基化合物的缩合得到一系列新的化合物,并采用MTT法对合成的衍生物进行9种人癌细胞毒活性研究,通过IC50来评价其抗肿瘤活性。结果得到的新化合物a、b、d和中间体c,分别为氢化九节龙皂苷Ⅰ、加氧九节龙皂苷Ⅰ、九节龙皂苷缩4-苄基-3-氨基硫脲和九节龙皂苷缩肼基二硫代甲酸甲酯;其中化合物a和中间体c对常见的9种人癌细胞IC50相比原皂苷均降低(P<0.05),说明其对肿瘤细胞的抑制能力较原皂苷增强。结论通过对九节龙皂苷I进行结构修饰,能够使其抗肿瘤活性增强。

Synthesis and cytotoxic activities of ardipusilloside I derivatives

Objective To seek novel compounds with better antineoplastic activities by modifying the structure of ardipusilloside I (ADS I) isolated from Ardisia pusilla. Methods A series of ADS I derivatives were synthesized through oxidation, reduction, and condensation on C-30 aldehyde group, and the antineoplastic activities of these compounds against nine kinds of human cancer cells were evaluated by MTT assay. Results Four derivatives a, b, d, and c were respectively named as hydrogenated ardipusilloside I, ardipusilloside I oxide, ardipusilloside 4-benzyl-3-thiosemicarbazide, ardipusilloside methyl hydrazinecarbodithioate. Compound a and c had lower IC₅₀ than the lead compound on nine kinds of human cancer cells (P< 0.05), which indicated that they could enhance the antineoplastic activities when compared with ADS I. Four derivatives of ADS I were synthesized, among which compounds a and c had lower IC₅₀ than the lead compound (P < 0.05). Conclusion Through structural modification of ADS I, the antineoplastic activities are enhanced.