Colchicine glycorandomization influences cytotoxicity and mechanism of action.
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.
Ahmed
Aqeel
A
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, USA.
Peters
Noël R
NR
Fitzgerald
Megan K
MK
Watson
James A
JA
Hoffmann
F Michael
FM
Thorson
Jon S
JS
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*
D000970:Antineoplastic Agents; D050257:Tubulin Modulators; D003078:Colchicine