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Colchicine glycorandomization influences cytotoxicity and mechanism of action
Aqeel Ahmed1, Noël R Peters, Megan K Fitzgerald
1Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, USA.
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.
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