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STEFANIA GRIMAUDO

3-Aryl-2-[1H-benzotriazol-1-yl]acrylonitriles: a novel class of potent tubulin inhibitors

  • Autori: Carta, A.; Briguglio, I.; Piras, S.; Boatto, G.; La Colla, P.; Loddo, R.; Tolomeo, M.; Grimaudo, S.; DI CRISTINA, A.; Pipitone, R.; Laurini, E.; Paneni, M.; Posocco, P.; Fermeglia, M.; Pricl, S.
  • Anno di pubblicazione: 2011
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • OA Link: http://hdl.handle.net/10447/73827

Abstract

During a screening for compounds that could act against Mycobacterium tuberculosis, a series of new cellular antiproliferative agents was identified. The most cytotoxic molecules were evaluated against a panel of human cell lines derived from hematological and solid human tumors. In particular, (E)-2-(1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-methoxyphenyl)acrylonitrile (1) was found to be of a potency comparable to etoposide and greater than 6-mercaptopurine in all cell lines tested. Accordingly, a synthesis of a new series of (E)-2-(5,6-dichloro-1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-R-phenyl)acrylonitriles was conducted in order to extend the studies of structure-activity relationship (SAR) for this class of molecules. With the aim to evaluate if 3-aryl-2-[1H-benzotriazol-1-yl]acrylonitriles were able to act like tubulin binding agents, the effects on cell cycle distribution of the most active compounds (1, 2a, 3 and 4) were analyzed in K562 cells. A detailed molecular modeling study of the putative binding mode of this series of compounds on tubulin is also reported.