Colchicine glycorandomization influences cytotoxicity and mechanism of action.
Aqeel Ahmed, Noël R Peters, Megan K Fitzgerald, James A Watson, F Michael Hoffmann, Jon S Thorson
Index: J. Am. Chem. Soc. 128(44) , 14224-5, (2006)
Full Text: HTML
Abstract
The reaction of 70 unprotected, diversely functionalized free reducing sugars with methoxyamine-appended colchicine led to the production of a 58-member glycorandomized library. High-throughput cytotoxicity assays revealed glycosylation to modulate specificity and potency. Library members were also identified which, unlike the parent natural product (a destabilizer), stabilized in vitro tubulin polymerization in a manner similar to taxol. This study highlights a simple extension of neoglycorandomization toward amine-bearing scaffolds and the potential benefit of glycosylating nonglycosylated natural products.
Related Compounds
Related Articles:
The role of thymidine phosphorylase, an angiogenic enzyme, in tumor progression.
2004-11-01
[Cancer Sci. 95(11) , 851-7, (2004)]
Synthesis and biological activity of hydroxylated analogues of KRN7000 (α-galactosylceramide).
2013-04-05
[Carbohydr. Res. 370 , 46-66, (2013)]
Warfarin glycosylation invokes a switch from anticoagulant to anticancer activity.
2011-08-01
[ChemMedChem 6(8) , 1347-50, (2011)]
Inhibition of metastasis of tumor cells overexpressing thymidine phosphorylase by 2-deoxy-L-ribose.
2004-03-01
[Cancer Res. 64(5) , 1794-801, (2004)]
Molecular basis for the inhibition of hypoxia-induced apoptosis by 2-deoxy-D-ribose.
2002-03-08
[Biochem. Biophys. Res. Commun. 291(4) , 806-12, (2002)]