title: Synthesis of anti-microtubule biaryls and preliminary evaluation as vascular-disrupting agents.
abstract: A series of new dibenzoxepines were synthesized in a straightforward and efficient manner through diastereoselective biaryl Suzuki-Miyaura coupling and Brønsted-acid-mediated cyclodehydration as key steps. The vascular-disrupting potential of these molecules was evaluated with various in vitro assays: inhibition of microtubule assembly, antiproliferative activity against cancer cell lines and normal endothelial cells, modification of endothelial cell morphology, and disruption of endothelial cell cords. Two of these compounds showed promising activities in these assays, with profiles similar to that of the reference drug NAC and markedly different from that of colchicine. Altogether, these results show that dibenzoxepines represent promising new leads for the development of more selective vascular-disrupting agents.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Joncour
authors.forename: Jian-Miao
authors.initials: JM
authors.lastname: Liu
authors.forename: Anne
authors.initials: A
authors.lastname: Décor
authors.forename: Sylviane
authors.initials: S
authors.lastname: Thoret
authors.forename: Joanna
authors.initials: J
authors.lastname: Wdzieczak-Bakala
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bignon
authors.forename: Olivier
authors.initials: O
authors.lastname: Baudoin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D014404:Tubulin / Q000737:chemistry*
chemical_list: D020533:Angiogenesis Inhibitors; D008024:Ligands; D014404:Tubulin