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

23 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 (US)
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
Externally published	Yes

Keywords

Regiochemistry
digitoxigenin
neoglycosylation
sugar

ASJC Scopus subject areas

Drug Discovery
Biochemistry
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 (US)",

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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

N2 - 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.

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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ER -

Influence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity

Abstract

Keywords

ASJC Scopus subject areas

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