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Synthesis and Biological Evaluation of Colchicine B‑Ring Analogues Tethered with Halogenated Benzyl Moieties

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journal contribution
posted on 27.12.2012, 00:00 by Laura Cosentino, Mariano Redondo-Horcajo, Ying Zhao, Ana Rita Santos, Kaniz F. Chowdury, Victoria Vinader, Qasem M. A. Abdallah, Hamdy Abdel-Rahman, Jérémie Fournier-Dit-Chabert, Steven D. Shnyder, Paul M. Loadman, Wei-shuo Fang, José Fernando Díaz, Isabel Barasoain, Philip A. Burns, Klaus Pors
Deacetylcolchicine was reacted with substituted benzyl halides to provide a library of compounds for biological analysis. Compound 7 (3,4-difluorobenzyl-N-aminocolchicine) was shown to possess cytotoxicity in cancer cell lines in the low nanomolar range. Significantly, it showed no loss of activity in the resistant A2780AD ovarian carcinoma cell line known to overexpress the ABCB1 drug transporter and was also unaffected by overexpression of class III β-tubulin in HeLa transfected cells.