Journal of the American Chemical Society 2006-11-08

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)

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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.