title: Design, synthesis and antiproliferative activities of biarylolefins based on polyhydroxylated and carbohydrate scaffolds.
abstract: A series of diversely substituted biarylolefins based on carbohydrate and dihydroxyethylene scaffolds were synthesized and evaluated for antiproliferative activity against a panel of human tumor cell lines. Among the thirty-five yet unknown biarylolefins prepared, six displayed potent antiproliferative activities with IC(50) values in the micromolar and submicromolar range. As a new type of antiproliferative agent, the most potent compound 26 showed an IC(50) value of 70 nM against SK-OV3 cell line (ovarian cancer). All the synthesized compounds exhibited a poor or modest tubulin polymerization inhibitory activity suggesting another mode of action for these compounds. Molecular docking simulations to the colchicine binding site of tubulin of representative compounds have been used to explain the lack of activity as inhibitors of tubulin polymerization.
authors.affiliation: UMR 7565 SRSMC, Nancy Université-CNRS, Groupe SUCRES, BP 239, F-54506 Nancy Vandœuvre, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Novoa
authors.forename: Nadia
authors.initials: N
authors.lastname: Pellegrini-Moïse
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bourg
authors.forename: Sylviane
authors.initials: S
authors.lastname: Thoret
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
authors.forename: Geneviève
authors.initials: G
authors.lastname: Aubert
authors.forename: Thierry
authors.initials: T
authors.lastname: Cresteil
authors.forename: Yves
authors.initials: Y
authors.lastname: Chapleur
mesh_terms: D000475:Alkenes / Q000737:chemistry / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D010051:Ovarian Neoplasms / Q000473:pathology*; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects
chemical_list: D000475:Alkenes; D002241:Carbohydrates; D014404:Tubulin