硫代秋水仙碱衍生物的合成和抗肿瘤活性(英文)

Synthesis and antitumor activity of nitrogen-based thiocolchicine derivatives

目的寻找高效低毒的秋水仙碱抗肿瘤衍生物。方法秋水仙碱首先被转化为硫代秋水仙碱,然后硫代秋水仙碱通过水解得到7-(N-脱乙酰基硫代秋水仙碱),最后经胺的酰化得到目标化合物。用1H NMR,IR,MS和HR-MS确证了这些衍生物的结构,MTT法评价了目标衍生物的细胞毒性;用对小鼠肝癌H22和宫颈癌U14的抑制率评价了衍生物的体内抗肿瘤活性。结果合成了12个硫代秋水仙碱新衍生物。结论尽管一些硫代秋水仙碱衍生物的体外细胞毒性强于秋水仙碱,然而小鼠体内抑瘤活性却较低。

Aim To search for colchicine derivatives which have high efficacy and low toxicity. Methods Colchicine was firstly converted into thiocolchicine, and then it was hydrolyzed to get 7-（ N- deacetylthiocolchicine）. At last, 7-（N-deacetylthiocolchicine） was amidated to get the target compounds. The chemical structure of these new derivatives was confirmed with ^1H NMR, IR, MS, and HR-MS. The cytotoxicity of the compounds was tested by MTT assay. Their in vivo antitumor activity was evaluated against mice tumor H22 and U14. Results Twelve thiocolchicine derivatives are new compounds. Conclusion In vitro antitumor activity has showed that some of these thiocolchicines possessed cytotoxic activity superior to colchicine. However, in vivo antitumor activity indicated that these derivatives have poor efficacy in mice.