论文部分内容阅读
目的:探索14-O-取代冬凌草甲素衍生物的合成及其抗肿瘤活性。方法:将二酸酐与冬凌草甲素14位羟基缩合,再与氨基酸酯进行酰胺化反应,合成14-O-取代冬凌草甲素衍生物;采用MTT法测试所有目标化合物体外对肿瘤细胞株(BGC-7901,SW-480,HL-60,BEL-7402,A549和B16)的细胞毒性以及化合物2c和2d对小鼠H22肝癌在体抗肿瘤活性。结果:合成了10个新的目标化合物,其结构均经IR,MS及1HNMR确证;生物活性初筛结果显示,化合物2c,2d和3e有较强的细胞毒活性;化合物2c和2d在体抗肿瘤活性大于环磷酰胺和冬凌草甲素。结论:14-O-取代冬凌草甲素衍生物2c,2d和3e作为潜在的抗肿瘤候选化合物值得进一步深入研究。
Objective: To explore the synthesis and antitumor activity of 14-O-substituted oridonin derivatives. METHODS: The 14-hydroxy group of the acid anhydride and the oridonin was condensed, and then amidated with the amino acid ester to synthesize the 14-O-substituted oridonin derivatives. All the target compounds were tested for the cytotoxicity against tumor cells (BGC-7901, SW-480, HL-60, BEL-7402, A549 and B16) and the in vivo antitumor activity of compounds 2c and 2d against mouse H22 hepatoma. RESULTS: Ten novel target compounds were synthesized and their structures were confirmed by IR, MS and 1HNMR. The preliminary bioassay results showed that compounds 2c, 2d and 3e had strong cytotoxic activity. Compounds 2c and 2d showed good anti- Tumor activity than cyclophosphamide and oridonin. CONCLUSION: The 14-O-substituted oridonin derivatives 2c, 2d and 3e are potential candidates for antitumor candidates and deserve further study.