Résumé
Our group has developed two innovative synthesis strategies that allowed to produce a 50‐member family of Imidazo[1,2a] quinoxaline compounds, named Imiqualines. Based on their strong anticancer potency and anti‐inflammatory properties, Imiqualines have recently been patented in the USA. The aim of the present study was to explore the mechanism of action involved in the cytotoxic effect of the leader Imiqualines, EAPB0203 and EAPB0503. Leader Imiqualines blocked A375 melanoma cells in the M phase of the cell cycle, inhibited purified tubulin polymerization, disrupted tubulin network in A375 and MCF7 cell lines, and bound tubulin on the colchicine binding site, based on in silico and in vitro studies. This finding lead us to test newly synthesized Imiqualines on the in silico model of tubulin. Preliminary results showed a correlation between binding affinity and cytotoxicity, encouraging us to develop this systematic predictive approach to enhance the structure activity relationship knowledge and identify new Imiqualine leaders. Support GEFLUC, SFPO‐ANP