cinnamamide analogs as inhibitors of protein tyrosine kinases

F. Buzzetti, M. G. Brasca, A. Crugnola, S. Fustinoni, A. Longo, S. Penco, P. Dalla Zonca, P. M. Comoglio

Research output: Contribution to journalArticlepeer-review


Protein tyrosine kinases (PTK) arc important signal transducing enzymes involved in the modulation of normal cellular growth and differentiation and have been associated with the etiology of various human cancers. The development of properly designed inhibitors, which block their function by interfering with the substrate binding, may therefore offer an unique target for selective anticancer chemotherapy. Here we describe synthesis and biochemical testing of a novel series of non-peptide PTK inhibitors which have as characteristic active pharmacophore the cinnamamide moiety. For testing we used an exogenous substrate kinase assay based on the phosphorylation of (Val)-angiotensin II with radiolabelled ATP by the catalytic domain of the PTK encoded by the v-abl oncogene (p45 v-abl). The most potent compounds were found in the class of 3-arylidene-2-oxindoles (II) with IC50 values in the 1μM range. Among these the 2-tetralylmethylene-, 4-quinolylmethylene-, 5-quinolylmethylene- and 3-indolylmethylene-2-oxindole compounds of formulae 16, 20, 21 and 24 respectively were selected for further investigation.

Original languageEnglish
Pages (from-to)615-636
Number of pages22
Issue number5
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmaceutical Science


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