Influence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity.
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.
Center for Pharmaceutical Research and Innovation and Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
Jianjun
J
Zhang
Center for Pharmaceutical Research and Innovation and Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
Larissa V
LV
Ponomareva
Center for Pharmaceutical Research and Innovation and Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
Nitin S
NS
Nandurkar
Center for Pharmaceutical Research and Innovation and Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
Yaxia
Y
Yuan
Center for Pharmaceutical Research and Innovation and Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
Lei
L
Fang
Center for Pharmaceutical Research and Innovation and Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
Chang-Guo
CG
Zhan
Center for Pharmaceutical Research and Innovation and Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
Jon S
JS
Thorson
Regiochemistry; digitoxigenin; neoglycosylation; sugar