Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10594287 | Bioorganic & Medicinal Chemistry Letters | 2012 | 4 Pages |
Abstract
Colchicine was modified at the 10-OCH3 position of the C-ring by reaction with heterocyclic amines or commercially available amines to afford a library of target colchicinoids in high yields (62-99%). Molecular modeling revealed that the incorporation of the linker groups led to a reduction in entropy and therefore binding affinity when compared with colchicine. Some colchicinoids were shown to be equicytotoxic with colchicine when evaluated in the DLD-1 colon cancer cells and retained activity in resistant A2780AD or HeLa cells with mutant Class III β-tubulin. Importantly, unlike colchicine, the analogues in this study are amenable for prodrug derivatisation and with potential for tumor-selective delivery.
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Authors
Jérémie Fournier-Dit-Chabert, Victoria Vinader, Ana Rita Santos, Mariano Redondo-Horcajo, Aurore Dreneau, Ramkrishna Basak, Laura Cosentino, Gemma Marston, Hamdy Abdel-Rahman, Paul M. Loadman, Steven D. Shnyder, José Fernando DÃaz, Isabel Barasoain,