title: Colchicine glycorandomization influences cytotoxicity and mechanism of action.
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.
authors.affiliation: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, USA.
authors.forename: Aqeel
authors.initials: A
authors.lastname: Ahmed
authors.forename: Noël R
authors.initials: NR
authors.lastname: Peters
authors.forename: Megan K
authors.initials: MK
authors.lastname: Fitzgerald
authors.forename: James A
authors.initials: JA
authors.lastname: Watson
authors.forename: F Michael
authors.initials: FM
authors.lastname: Hoffmann
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology; D003078:Colchicine / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D020128:Inhibitory Concentration 50; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D050257:Tubulin Modulators; D003078:Colchicine