Affiliation: Laboratoire d’innovation therapeutique, UMR 7200, Faculte de Pharmacie, Université de Strasbourg, 74-route du Rhin, BP 60024 - 67401 ILLKIRCH Cedex – France.
Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combretastatin A-4 analogues. Our objective was to overcome the spontaneous cis to trans isomerization of the compound. We therefore replaced the cis-double bond with a pyridazine ring. The antiproliferative activity of the novel analogues was evaluated against four human cancer cell lines (HL-60, MDAMB- 435, SF-295 and HCT-8). We found that the analogues had little activity either against selected cell lines or against purified tubulin. Molecular modeling studies may account for their inactivity.