Portal de Periódicos da CAPES

Design, synthesis and anticancer properties of 5-arylbenzoxepins as conformationally restricted iso combretastatin A-4 analogs

2013; Elsevier BV; Volume: 62; Linguagem: Inglês

10.1016/j.ejmech.2012.12.042

1768-3254

Evelia Rasolofonjatovo, Olivier Provot, Abdallah Hamzé, Jordi Rodrigo, Jérôme Bignon, Joanna Wdzieczak‐Bakala, C. Lenoir, Déborah Desravines, Joëlle Dubois, Jean‐Daniel Brion, Mouâd Alami,

Microbial Natural Products and Biosynthesis

A series of novel benzoxepins 6 was designed and prepared as rigid-isoCA-4 analogs according to a convergent strategy using the coupling of N-tosylhydrazones with aryl iodides under palladium catalysis. The most potent compound 6b, having the greatest resemblance to CA-4 and isoCA-4 displayed antiproliferative activity at nanomolar concentrations against various cancer cell lines and inhibited tubulin assembly at a micromolar range. In addition, benzoxepin 6b led to the arrest of HCT116, K562, H1299 and MDA-MB231 cancer cell lines in the G2/M phase of the cell cycle, and strongly induced apoptosis at low concentrations. Docking studies demonstrated that benzoxepin 6b adopt an orientation similar to that of isoCA-4 at the colchicine binding site on β-tubulin.