Mohamed Elagawany, Martine Schmitt, Adel Ghiaty, A. Sh. El-Etrawy, Mohamed A. Ibrahim, Frederic Bihel, Aline Borba Sbardelotto, Claudia Pessoa, Tam Luong Nguyen, Ernest Hamel and Jean Jacques Bourguignon Pages 1133 - 1140 ( 8 )
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.
Pyridazine, Combretastatin A-4, Cytotoxicity, Suzuki-Miyaura cross coupling, Anticancer agent and Tubulin activity.
, , , , , , , , , , Laboratoire d’innovation therapeutique, UMR 7200, Faculte de Pharmacie, Université de Strasbourg, 74-route du Rhin, BP 60024 - 67401 ILLKIRCH Cedex – France.