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Influence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity.

ABSTRACT: 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(+),K(+)-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.

SUBMITTER: Zhang J

PROVIDER: S-EPMC4601055 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Influence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity.

Zhang Jianjun J Ponomareva Larissa V LV Nandurkar Nitin S NS Yuan Yaxia Y Fang Lei L Zhan Chang-Guo CG Thorson Jon S JS

ACS medicinal chemistry letters 20150812 10

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(+),K(+)-ATPase docked models correlated with increased anticancer potency. This study presents a preliminary model for potential further warh ...[more]

PMID: 26487911

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