Influence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity
Jianjun Zhang1, Larissa V Ponomareva1, Nitin S Nandurkar1
1Center for Pharmaceutical Research and Innovation and Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
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.
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