Colchicine glycorandomization influences cytotoxicity and mechanism of action

被引：74
作者：
Ahmed, Aqeel
Peters, Noel R.
Fitzgeraldo, Megan K.
Watson, James A., Jr.
Hoffmann, F. Michael
Thorson, Jon S. [1 ]
机构：
[1] Univ Wisconsin, Sch Pharm, Pharmaceut Sci Div, Madison, WI 53705 USA
[2] Keck Univ Wisconsin, Ctr Comprehens Canc, Small Mol Screening Facil, Madison, WI 53705 USA
来源：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2006年 / 128卷 / 44期
关键词：
D O I：
10.1021/ja064686s
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
The reaction of 70 unprotected, diversely functionalized free reducing sugars with methoxyamine-appended colchicine led to the production of a 58-member glycorandomized library. High-throughput cytotoxicity assays revealed glycosylation to modulate specificity and potency. Library members were also identified which, unlike the parent natural product (a destabilizer), stabilized in vitro tubulin polymerization in a manner similar to taxol. This study highlights a simple extension of neoglycorandomization toward amine-bearing scaffolds and the potential benefit of glycosylating nonglycosylated natural products. Copyright © 2006 American Chemical Society.
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收藏
页码：14224 / 14225
页数：2
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