title: Synthesis and antiproliferative effects of 5,6-disubstituted Pyridazin-3(2H)-ones designed as conformationally constrained combretastatin A-4 Analogues.
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.
authors.affiliation: Laboratoire'innovation Therapeutique, UMR 7200, Faculte de Pharmacie, Université de Strasbourg, 74-route du Rhin, BP 60024 - 67401 ILLKIRCH Cedex - France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elagawany
authors.forename: Martine
authors.initials: M
authors.lastname: Schmitt
authors.forename: Adel
authors.initials: A
authors.lastname: Ghiaty
authors.forename: A Sh
authors.initials: ASh
authors.lastname: El-Etrawy
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ibrahim
authors.forename: Frederic
authors.initials: F
authors.lastname: Bihel
authors.forename: Aline Borba
authors.initials: AB
authors.lastname: Sbardelotto
authors.forename: Claudia
authors.initials: C
authors.lastname: Pessoa
authors.forename: Tam Luong
authors.initials: TL
authors.lastname: Nguyen
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Bourguignon
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011724:Pyridazines; D013267:Stilbenes; D014404:Tubulin; C062482:pyridazine; C058728:fosbretabulin