Portal de Periódicos da CAPES

Discovery of azaisoerianin derivatives as potential antitumors agents

2014; Elsevier BV; Volume: 78; Linguagem: Inglês

10.1016/j.ejmech.2014.03.032

1768-3254

Mohamed Ali Soussi, Olivier Provot, Guillaume Bernadat, Jérôme Bignon, Joanna Wdzieczak‐Bakala, Déborah Desravines, Joëlle Dubois, Jean‐Daniel Brion, Samir Messaoudi, Mouâd Alami,

Cancer therapeutics and mechanisms

A series of N-methyl-diarylamines 2 was designed and synthesized as a novel class of CA-4 and isoCA-4 analogues. Compounds 2b and 2m showed excellent antiproliferative activity with mean GI50 values at a nanomolar level in a diverse set of human cancer cells. These compounds also inhibited tubulin assembly at a micromolar range, arrested the cellular cycle in the G2/M phase and induced apoptosis at very low concentrations. Preliminary in vitro results revealed that 2b and 2m displayed substantial efficacy as potent antivascular agents. Docking studies indicates that these lead compounds showed a binding mode similar to those observed with isoCA-4 at the colchicine binding site of tubulin.