title: Synthesis and biological evaluation of (3,4,5-trimethoxyphenyl)indol-3-ylmethane derivatives as potential antivascular agents.
abstract: Combretastatin A-4 (CSA-4), a stilbene derivative, is a potent vascular disrupting agent (VDA) with the structural requirement of a cis-configuration to maintain a molecular geometry and a correct orientation of both phenyl groups. A series of indolic analogues of CSA-4 was synthesized by means of an efficient strategy. Six compounds (20b, 25b-27b, 32b, and 35b) were identified as potent inhibitors of tubulin polymerization and also displayed cytotoxic activities on B16 melanoma cells at a nanomolar level. Both activities were well correlated with the ability to induce morphological changes of EA.hy 926 endothelial cells. In conclusion, the cis-stilbene skeleton of CSA-4 could conveniently be replaced by the 3-aroylindolic moiety, thus avoiding any isomerization leading to inactive trans compounds.
authors.affiliation: Université Paris 5, Faculté des Sciences Pharmaceutiques et Biologiques, UMR 8638 CNRS, Laboratoire de Pharmacognosie, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Dupeyre
authors.forename: Guy G
authors.initials: GG
authors.lastname: Chabot
authors.forename: Sylviane
authors.initials: S
authors.lastname: Thoret
authors.forename: Xavier
authors.initials: X
authors.lastname: Cachet
authors.forename: Johanne
authors.initials: J
authors.lastname: Seguin
authors.forename: Daniel
authors.initials: D
authors.lastname: Guénard
authors.forename: François
authors.initials: F
authors.lastname: Tillequin
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.forename: Michel
authors.initials: M
authors.lastname: Koch
authors.forename: Sylvie
authors.initials: S
authors.lastname: Michel
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D008546:Melanoma, Experimental; D051379:Mice; D013267:Stilbenes / Q000737:chemistry*; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D013267:Stilbenes; D014404:Tubulin; C058728:fosbretabulin