title: Synthesis and biological evaluation of 4-arylcoumarin analogues of combretastatins.
abstract: A series of A-ring polymethoxylated neoflavonoids was prepared by ligand coupling reactions involving either Suzuki or Stille reactions. Cytotoxicity studies indicated a potent activity against a CEM leukemia cell line for the compounds presenting a substitution pattern related to that of combretastatin A-4. The two compounds having a 3'-OH and a 4'-OCH(3) substituents on the 4-phenyl B-ring have no effect on human topoisomerases I and II but potently inhibit, in vitro, microtubule assembly. At the cell level, the active compounds were characterized as proapoptotic agents, but they can also trigger cell death via a nonapoptotic pathway.
authors.affiliation: INSERM U-524 et Laboratoire de Pharmacologie antitumorale du Centre Oscar Lambret, Institut de Recherches sur le Cancer, Place de Verdun, 59045 Lille, France. bailly@lille.inserm.fr
authors.forename: Christian
authors.initials: C
authors.lastname: Bailly
authors.forename: Christine
authors.initials: C
authors.lastname: Bal
authors.forename: Pascale
authors.initials: P
authors.lastname: Barbier
authors.forename: Sébastien
authors.initials: S
authors.lastname: Combes
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Finet
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Hildebrand
authors.forename: Vincent
authors.initials: V
authors.lastname: Peyrot
authors.forename: Nicole
authors.initials: N
authors.lastname: Wattez
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001704:Biopolymers; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000737:chemistry; D004250:DNA Topoisomerases, Type II / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014404:Tubulin / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001704:Biopolymers; D013267:Stilbenes; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014404:Tubulin; D020169:Caspases; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; C058728:fosbretabulin