title: Synthesis and biological evaluation of polymethoxylated 4-heteroarylcoumarins as tubulin assembly inhibitor.
abstract: A series of syn-restricted polymethoxylated 4-heteroarylcoumarins--the isostuctural analogs of combretastatin A-4--was synthesized by Suzuki-Miyaura cross-coupling reaction and evaluated for antiproliferative activity. The 4-(1-methyl-1H-indol-5-yl)chromen-2-ones exhibit a potent cytotoxicity against HBL100 epithelial cell line with an IC(50) value amounting to 0.098 and 0.078 microM, respectively. The two compounds, having an indolyl moiety, potent inhibit in vitro microtubule assembly with a substoichiometric mode of action. A structure-activity relationship was discussed and the indolyl moiety was proved to be a good surrogate for the 3-hydroxy-4-methoxyphenyl ring of CA-4.
authors.affiliation: Department of Chemistry, Moscow State Lomonosov University, Vorobyevy Gory, 119992 Moscow, Russia.
authors.forename: Olga G
authors.initials: OG
authors.lastname: Ganina
authors.forename: Etienne
authors.initials: E
authors.lastname: Daras
authors.forename: Véronique
authors.initials: V
authors.lastname: Bourgarel-Rey
authors.forename: Vincent
authors.initials: V
authors.lastname: Peyrot
authors.forename: Alexey N
authors.initials: AN
authors.lastname: Andresyuk
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Finet
authors.forename: Alexey Yu
authors.initials: AY
authors.lastname: Fedorov
authors.forename: Irina P
authors.initials: IP
authors.lastname: Beletskaya
authors.forename: Sébastien
authors.initials: S
authors.lastname: Combes
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D013267:Stilbenes / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D003432:Cross-Linking Reagents; D013267:Stilbenes; D050257:Tubulin Modulators; C058728:fosbretabulin