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

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 , Jean Jacques Bourguignon .

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 13 , Issue 7 , 2013

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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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Article Details

Year: 2013
Page: [1133 - 1140]
Pages: 8
DOI: 10.2174/1871520611313070018
Price: $58

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