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

Rosaria Maria Pipitone, Stefania Grimaudo, Paola Posocco, Erik Laurini, Paolo La Colla, Roberta Loddo, Irene Briguglio, Giampiero Boatto, Maria Silvia Paneni, Sandra Piras, Sabrina Pricl, Antonio Carta, Maurizio Fermeglia, Antonietta Di Cristina

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)4151-4167
Number of pages17
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 2011

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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