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Design, synthesis and anticancer properties of IsoCombretaQuinolines as potent tubulin assembly inhibitors

2016; Elsevier BV; Volume: 127; Linguagem: Inglês

10.1016/j.ejmech.2016.11.012

1768-3254

Ilhem Khelifi, Timothée Naret, Dolor Renko, Abdallah Hamzé, Guillaume Bernadat, Jérôme Bignon, C. Lenoir, Joëlle Dubois, Jean‐Daniel Brion, Olivier Provot, Mouâd Alami,

Cancer therapeutics and mechanisms

The synthesis and evaluation of a new series of IsoCombretaQuinolines (IsoCoQuines) 2 with a 2-substituted-quinoline in place of the 3,4,5-trimethoxyphenyl ring present in isoCA-4 and CA-4 are described. Most of these compounds displayed a potent cytotoxic activity (IC50 < 10 nM) against a panel of five human cancer cell lines and inhibited tubulin assembly at a micromolar level. The most potent analogue 2b, having a 3-hydroxy-4-methoxyphenyl as B-ring, led to cell cycle arrest in G2/M phase. Docking studies indicate that 2b showed a binding mode comparable to those previously observed with quinazoline analogous (IsoCoQ) and with isoCA-4 at the colchicine binding site of tubulin.