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Le Centre de Recherche en Cancérologie de Marseille fête ses 50 ans ! -

Oct 2008 Bioorganic & medicinal chemistry

Synthesis and biological evaluation of polymethoxylated 4-heteroarylcoumarins as tubulin assembly inhibitor.


Ganina OG, Daras E, Bourgarel-Rey V, Peyrot V, Andresyuk AN, Finet JP, Fedorov AY, Beletskaya IP, Combes S


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.

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