Synthesis and Biological Evaluation of Colchicine B-Ring Analogues Tethered with Halogenated Benzyl Moieties
Synthesis and Biological Evaluation of Colchicine B-Ring Analogues Tethered with Halogenated Benzyl Moieties
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卤代苄基秋水仙碱 B 环类似物的合成和生物学评价
DOI：
10.1021/jm301151t
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发表时间：
2012-12-27
影响因子：
7.3
通讯作者：
Pors, Klaus
中科院分区：
文献类型：
--
作者：
Cosentino, Laura;Redondo-Horcajo, Mariano;Pors, Klaus
脱乙酰秋水仙碱与取代的苄基卤反应，提供用于生物分析的化合物库。化合物 7（3,4-二氟苄基-N-氨基秋水仙碱）在低纳摩尔范围内对癌细胞系具有细胞毒性。值得注意的是，它在已知过度表达 ABCB1 药物转运蛋白的耐药 A2780AD 卵巢癌细胞系中没有表现出活性丧失，并且也不受 HeLa 转染细胞中 III 类 β-微管蛋白过度表达的影响。
Deacetylcolchicine was reacted with substituted benzyl halides to provide a library of compounds for biological analysis. Compound 7 (3,4-difluorobenzyl-N-aminocolchicine) was shown to possess cytotoxicity in cancer cell lines in the low nanomolar range. Significantly, it showed no loss of activity in the resistant A2780AD ovarian carcinoma cell line known to overexpress the ABCB1 drug transporter and was also unaffected by overexpression of class III beta-tubulin in HeLa transfected cells.