Influence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity
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- 作者：Jianjun Zhang ; Larissa V. Ponomareva ; Nitin S. Nandurkar ; Yaxia Yuan ; Lei Fang ; Chang-Guo Zhan ; Jon S. Thorson
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2015
- 出版时间：October 8, 2015
- 年：2015
- 卷：6
- 期：10
- 页码：1053-1058
- 全文大小：482K
- ISSN：1948-5875
文摘
The synthesis of a set of digitoxigenin neogluco/xylosides and corresponding study of their anticancer SAR revealed sugar amine regiochemistry has a dramatic effect upon activity. Specifically, this study noted sugar 3-amino followed by 4-amino-substitution to be most advantageous where the solvent accessibility of the appended amine within neoglycoside-Na<sup>+sup>,K<sup>+sup>-ATPase docked models correlated with increased anticancer potency. This study presents a preliminary model for potential further warhead optimization in the context of antibody-directed steroidal glycosides and extends the demonstrated compatibility of aminosugars in the context of neoglycosylation.