异甜菊醇衍生物的合成及抗肿瘤活性

Synthesis and antitumor activity of isosteviol derivatives

摘要: 对异甜菊醇C-环、D-环进行结构修饰与改造，同时将其C₁₉-COOH成酯，设计并合成了 9个未见文献报道的新化合物( 5 ~ 13 )，所有目标化合物的结构均经ESI-MS，IR，¹H NMR确定。采用MTT法测试了目标化合物对HCT116，Huh7，SW620及HepG2等细胞的抗肿瘤活性。初步研究结果表明，化合物 13 表现出对人结肠癌HCT116细胞具有选择性抑制作用(IC₅₀=3.57 μmol/L)，与阳性对照舒尼替尼(sunitininb)(IC₅₀=5.62 μmol/L)活性相当，化合物 10 对HCT116，Huh7，SW620均有较强抑制作用。

Abstract: To explore isosteviol derivatives with more potent antitumor activity, nine novel C-ring and/or D-ring modified compounds( 5 - 13 )were designed and synthesized. The structures of the derivatives were identified by IR, 1H NMR and MS. Cytotoxicity of all the target compounds was tested by MTT method in HepG2, HCT116, Huh7 and SW620 cells, and the preliminary results showed that compound 13 exhibited a selective cytotoxicity(IC₅₀=3. 57 μmol/L)against HCT116 cell, and was comparable to that of sunitininb(IC₅₀=5. 62 μmol/L). Compound 10 has good inhibitory effects on HCT116, Huh7, SW620 cell lines.