Synthesis and Biological Evaluation of Furanoallocolchicinoids
Synthesis and Biological Evaluation of Furanoallocolchicinoids
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DOI：
10.1021/jm501678w
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发表时间：
2015-01-22
影响因子：
7.3
通讯作者：
Fedorov, Alexey Yu.
中科院分区：
文献类型：
--
作者：
Voitovich, Yuliya V.;Shegravina, Ekaterina S.;Fedorov, Alexey Yu.
以市购秋水仙碱为原料，采用三步反应法制备了一系列构象灵活的呋喃衍生的异秋水仙素。细胞毒性研究表明，这两种化合物对人上皮细胞和淋巴细胞（AsPC-1、HEK293和Jurkat）以及Wnt-1相关的小鼠上皮细胞W1308具有强效活性。体外实验结果表明，这些化合物的主要作用是诱导细胞周期阻滞在G2/M期，这是微管蛋白有效结合的直接结果。用C57BL/6小鼠接种Wnt-1肿瘤细胞，体内检测最强效呋喃异秋水仙素10c对肿瘤生长有明显抑制作用。
A series of conformationally flexible furan-derived allocolchicinoids was prepared from commercially available colchicine in good to excellent yields using a three-step reaction sequence. Cytotoxicity studies indicated the potent activity of two compounds against human epithelial and lymphoid cell lines (AsPC-1, HEK293, and Jurkat) as well as against Wnt-1 related murine epithelial cell line W1308. The results of in vitro experiments demonstrated that the major effect of these compounds was the induction of cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding. In vivo testing of the most potent furanoallocolchicinoid 10c using C57BL/6 mice inoculated with Wnt-1 tumor cells indicated significant inhibition of the tumor growth.