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

5 páginas, 3 figuras, 3 tablas, 1 esquema -- PAGS nros. 11062-11066Deacetylcolchicine 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 cellsK.P. was supported by YCR Program Grant, EPSRC Science Bridge (Grant EP/G042365/1), FCT (Grant SFRH/BD/46871/2008) and J.F.D. by Grant BIO2010-16351 from Ministerio de Economia y Competitividad and Grant S2010/BMD-2457 BIPEDD2 from Comunidad Autónoma de Madrid, Spain. Parental HeLa and transfected β-III cervix carcinoma cell lines were a kindly gift from Prof. Richard F. Ludueña (Biochemical Dept., The University of Texas Health Science Center, TX, U.S.)Peer reviewe