Synthesis and Antiproliferative Effects of 5,6-Disubstituted Pyridazin-3(2H)-ones Designed as Conformationally Constrained Combretastatin A-4 Analogues
A. Sh. El-Etrawy,
Mohamed A. Ibrahim,
Aline Borba Sbardelotto,
Tam Luong Nguyen,
Jean Jacques Bourguignon.
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.
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