呋喃鬼臼毒素衍生物及其抗肿瘤活性研究

Synthesis and evaluation of furanoid podophyllotoxin derivatives with anticancer activity

目的:获得抗肿瘤活性更强的鬼臼毒素衍生物。方法:以鬼臼毒素为起始原料,通过把取代呋喃和鬼臼毒素拼接,设计并合成5个4β-N-取代呋喃鬼臼毒素衍生物,目标产物的结构通过1H-NMR,13C-NMR和HRMS的确证,同时采用MTT法评价新化合物对He La,K562和K562/A02的细胞毒活性。结果:合成的5个化合物均具有确切的细胞毒活性,其中化合物7c和11b对于耐药肿瘤细胞K562/A02的活性明显优于阳性对照依托伯苷。结论:把取代呋喃连接到鬼臼毒素可以增加抗肿瘤活性。

Objective： To acquire novel podophyllotoxin derivatives with higher antitumor activity. Methods：The podophyllotoxin derivatives were synthesized using podophyllotoxin as the starting material through substituted furfuran and success split joint podophyllotoxin. Five rift-N-substituted furfuran podophyllotoxin derivatives were designed, synthesized, and confirmed by 1H-NMR, 13C-NMR and HRMS, In vitro, cytotoxieities were tested against three human tumor cells （HeLa, K562, K562/A02） by MTI＇. Results： All compounds showed improved activities against HeLa and K562 when compared with VP-16. In particular, compound 7c, 1 lb exhibited the most potent activity toward drug-resistant K562/A02 cells, as compared to VP-16. Conclusion： Substituted furan connected to the podophyllotoxin could increase antitumor activity.