丹参新酮C环酚酯衍生物的设计合成及抗肿瘤活性研究

目的：通过对丹参新酮C环邻醌位点的结构修饰,改变其脂水分配系数(CLogP),获得系列丹参新酮酚酯衍生物,进而评价其抗肿瘤活性。方法：采用氢化还原、酰化、脱保护基等方法对丹参新酮的邻醌位点进行修饰,通过引入不同酸酐、氨基酸取代基,得到丹参新酮C环酚酯衍生物,在此基础上以前列腺癌Lncap和Du145细胞株对部分化合物进行抗肿瘤活性评价。结果：共合成了9个新的丹参新酮酚酯衍生物,其中1个化合物表现出较好的抗肿瘤活性。结论：脂水分配系数的改变对丹参新酮衍生物抗肿瘤活性影响很大,适当提高水溶性,有助于增强其抗肿瘤活性,改善成药性。

Design, Synthesis and Anti-tumor Activity Evaluation of New Miltirone Esters Derived From Ring C

OBJECTIVE To synthesize miltirone ester derivatives with various lipid/water partition coefficients based on modification of quinone group, and evaluate the anti-tumor activities. METHODS Hydrogenation reduction, anhydride acylation and deprotection of Boc-groups were used to modify abietane o-quinone sites through introducing different anhydride, amino acid substituents and different miltirone C cyclic phenol ester derivatives were synthesized, on the basis of this, the anti-tumor activity of parts of compounds were evaluated by prostate cancer Lncap and Du145 cell lines. RESULTS Totally 9 miltirone derivatives were synthesized, among which 1 compound exhibited enhanced in vitro anti-tumor activities against Lncap and Du145 cell lines compared with miltirone. CONCLUSION The lipid/water partition coefficient has great influence on the anti-tumor activity of miltirone derivatives, structure modification to improve the hydrophilicity of miltirone can effectively enhance it''s antitumor activity.