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Wang HY, Xin W, Zhou M, et al. Stereochemical survey of digitoxin monosaccharides: new anticancer analogues with enhanced apoptotic activity and growth inhibitory effect on human non-small cell lung cancer cell. ACS Med Chem Lett. 2011;2(1):73-78doi: 10.1021/ml100219d.
Wang, H. Y., Xin, W., Zhou, M., Stueckle, T. A., Rojanasakul, Y., & O'Doherty, G. A. (2011). Stereochemical survey of digitoxin monosaccharides: new anticancer analogues with enhanced apoptotic activity and growth inhibitory effect on human non-small cell lung cancer cell. ACS medicinal chemistry letters, 2(1), 73-78. https://doi.org/10.1021/ml100219d
Wang, Hua-Yu Leo, et al. "Stereochemical survey of digitoxin monosaccharides: new anticancer analogues with enhanced apoptotic activity and growth inhibitory effect on human non-small cell lung cancer cell." ACS medicinal chemistry letters vol. 2,1 (2011): 73-78. doi: https://doi.org/10.1021/ml100219d
Wang HY, Xin W, Zhou M, Stueckle TA, Rojanasakul Y, O'Doherty GA. Stereochemical survey of digitoxin monosaccharides: new anticancer analogues with enhanced apoptotic activity and growth inhibitory effect on human non-small cell lung cancer cell. ACS Med Chem Lett. 2011 Jan 13;2(1):73-78. doi: 10.1021/ml100219d. PMID: 21643465; PMCID: PMC3105780.
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ACS Med Chem Lett. 2011 Jan 13;2(1):73-78. doi: 10.1021/ml100219d.

Stereochemical survey of digitoxin monosaccharides: new anticancer analogues with enhanced apoptotic activity and growth inhibitory effect on human non-small cell lung cancer cell.

ACS medicinal chemistry letters

Hua-Yu Leo Wang, Wenjun Xin, Maoquan Zhou, Todd A Stueckle, Yon Rojanasakul, George A O'Doherty

Affiliations

  1. Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115.

PMID: 21643465 PMCID: PMC3105780 DOI: 10.1021/ml100219d

Abstract

A stereochemically diverse array of monosaccharide analogues of the trisaccharide based cardiac glycoside natural product digitoxin has been synthesized using a de novo asymmetric approach. The analogues were tested for cytotoxicity against the NCI panel of 60 human cancer cell lines and in more detail against non-small cell human lung cancer cells (NCI-H460). The results were compared with digitoxin and its aglycone digitoxigenin. Three novel digitoxin monosaccharide analogues with β-d-digitoxose, α-l-rhamnose, and α-l-amicetose sugar moieties showed excellent selectivity and activity. Further investigation revealed that digitoxin α-l-rhamnose and α-l-amicetose analogues displayed similar anti-proliferation effects, but with at least 5-fold greater potency in apoptosis induction than digitoxin against NCI-H460. This study demonstrates the ability to improve the digitoxin anti-cancer activity by modification of the stereochemistry and substitution of the carbohydrate moiety of this known cardiac drug.

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