Influence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity

Jianjun Zhang; Larissa V. Ponomareva; Nitin S. Nandurkar; Yaxia Yuan; Lei Fang; Chang Guo Zhan; Jon S. Thorson

doi:10.1021/acsmedchemlett.5b00120

Influence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity

Jianjun Zhang
, Larissa V. Ponomareva
, Nitin S. Nandurkar
, Yaxia Yuan
, Lei Fang
, Chang Guo Zhan
, Jon S. Thorson

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Original language	English
Pages (from-to)	1053-1058
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	6
Issue number	10
DOIs	https://doi.org/10.1021/acsmedchemlett.5b00120
State	Published - Oct 8 2015

Bibliographical note

Publisher Copyright:
© 2015 American Chemical Society.

Funding

Funders	Funder number
National Center for Advancing Translational Sciences (NCATS)	UL1TR000117
National Institutes of Health (NIH)	R37 AI52218

Keywords

Regiochemistry
digitoxigenin
neoglycosylation
sugar

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/acsmedchemlett.5b00120

Cite this

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title = "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.",

keywords = "Regiochemistry, digitoxigenin, neoglycosylation, sugar",

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doi = "10.1021/acsmedchemlett.5b00120",

language = "English",

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AU - Zhang, Jianjun

AU - Ponomareva, Larissa V.

AU - Nandurkar, Nitin S.

AU - Yuan, Yaxia

AU - Fang, Lei

AU - Zhan, Chang Guo

AU - Thorson, Jon S.

PY - 2015/10/8

Y1 - 2015/10/8

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AB - 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.

KW - Regiochemistry

KW - digitoxigenin

KW - neoglycosylation

KW - sugar

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JO - ACS Medicinal Chemistry Letters

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ER -

Influence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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