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Anti-Cancer Agents in Medicinal Chemistry

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

DOI: 10.2174/1871520611313070018

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

Page: [1133 - 1140] Pages: 8

  • * (Excluding Mailing and Handling)

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.

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