title: New antitubulin derivatives in the combretastatin A4 series: synthesis and biological evaluation.
abstract: Two series of combretastatin A4 derivatives (acrylamide=carboxamide and carbamate) were synthesized in order to improve the water solubility and stabilize the cis-configuration of the double bond. Their cytotoxic effects were evaluated against MCF-7, KB-3-1 and IGROV human cancer cell lines, as well as their inhibitory activity on tubulin polymerization. Results were compared to those of carboxamide 1, chosen as reference. Potent inhibitions were observed on both tests in the carboxamide series, particularly for compound 4d bearing a fluorine group in replacement of the 3-hydroxyl of CA4. In contrast, most of the carbamates were either inactive or displayed only moderate cytotoxicities. Interestingly, a submicromolar IC(50) was measured on MCF-7 cells for 6g, although this compound was totally devoid of antitubulin activity.
authors.affiliation: Laboratoire de Pharmacognosie, Université René Descartes (Paris 5), CNRS UMR 8638, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Borrel
authors.forename: Sylviane
authors.initials: S
authors.lastname: Thoret
authors.forename: Xavier
authors.initials: X
authors.lastname: Cachet
authors.forename: Daniel
authors.initials: D
authors.lastname: Guénard
authors.forename: François
authors.initials: F
authors.lastname: Tillequin
authors.forename: Michel
authors.initials: M
authors.lastname: Koch
authors.forename: Sylvie
authors.initials: S
authors.lastname: Michel
mesh_terms: D001704:Biopolymers; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013057:Spectrum Analysis / Q000379:methods; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators
chemical_list: D001704:Biopolymers; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; C058728:fosbretabulin