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.
Keywords: Pyridazine, Combretastatin A-4, Cytotoxicity, Suzuki-Miyaura cross coupling, Anticancer agent and Tubulin activity.
Rights & PermissionsPrintExport
Published on: 30 June, 2013
Page: [1133 - 1140]