5555-55-5Relevant academic research and scientific papers
Synthesis and biological evaluation of RON-neoglycosides as tumor cytotoxins
Langenhan, Joseph M.,Endo, Matthew M.,Engle, Jeffrey M.,Fukumoto, Liane L.,Rogalsky, Derek R.,Slevin, Lauren K.,Fay, Lindsay R.,Lucker, Ryan W.,Rohlfing, James R.,Smith, Kyle R.,Tjaden, Anja E.,Werner, Halina M.
, p. 2663 - 2676 (2012/01/07)
Cardenolides such as digitoxin have been shown to inhibit cancer cell growth, to reduce cancer metastasis, and to induce apoptosis in tumor cells. Among the most potent digitoxin-based cytotoxins identified to date are MeON-neoglycosides generated via oxyamine neoglycosylation. Here, we report our studies of oxyamine neoglycosylation aimed at facilitating the elucidation of linkage-diversified digitoxin neoglycoside structure-activity relationships. We identified conditions suitable for the convenient synthesis of digitoxin neoglycosides and found that sugar structure, rather than RON-glycosidic linkage, exerts the strongest influence on neoglycoside yield and stereochemistry. We synthesized a library of digitoxin neoglycosides and assessed their cytotoxicity against eight human cancer cell lines. Consistent with previous findings, our data show that the structure of RON-neoglycosidic linkages influences both the potency and selectivity of digitoxin neoglycosides.
