Synthesis and Antiproliferative Effects of 5,6-Disubstituted Pyridazin-3(2H)-ones Designed as Conformationally Constrained Combretastatin A-4 Analogues

Title:Synthesis and Antiproliferative Effects of 5,6-Disubstituted Pyridazin-3(2H)-ones Designed as Conformationally Constrained Combretastatin A-4 Analogues

Volume: 13 Issue: 7

Author(s): 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

Affiliation:

Keywords: Pyridazine, Combretastatin A-4, Cytotoxicity, Suzuki-Miyaura cross coupling, Anticancer agent and Tubulin activity.

Abstract: 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.

Cite this article as:

Elagawany Mohamed, Schmitt Martine, Ghiaty Adel, El-Etrawy Sh. A., Ibrahim A. Mohamed, Bihel Frederic, Sbardelotto Borba Aline, Pessoa Claudia, Nguyen Luong Tam, Hamel Ernest and Bourguignon Jacques Jean, Synthesis and Antiproliferative Effects of 5,6-Disubstituted Pyridazin-3(2H)-ones Designed as Conformationally Constrained Combretastatin A-4 Analogues, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (7) . https://dx.doi.org/10.2174/1871520611313070018