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Synthesis and Evaluation of the Anticancer and Trypanocidal Activities of Boronic Tyrphostins

Molecules containing an (cyanovinyl)arene moiety are known as tyrphostins because of their ability to inhibit proteins from the tyrosine kinase family, an interesting target for the development of anticancer and trypanocidal drugs. In the present work, (E)‐(cyanovinyl)benzeneboronic acids were synth...

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Published in:ChemMedChem 2018-07, Vol.13 (14), p.1395-1404
Main Authors: Hiller, Noemi de J., Silva, Nayane A. A. e, Faria, Robson X., Souza, André Luís A., Resende, Jackson A. L. C., Borges Farias, André, Correia Romeiro, Nelilma, de Luna Martins, Daniela
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Language:English
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Summary:Molecules containing an (cyanovinyl)arene moiety are known as tyrphostins because of their ability to inhibit proteins from the tyrosine kinase family, an interesting target for the development of anticancer and trypanocidal drugs. In the present work, (E)‐(cyanovinyl)benzeneboronic acids were synthesized by Knoevenagel condensations without the use of any catalysts in water through a simple protocol that completely avoided the use of organic solvents in the synthesis and workup process. The in vitro anticancer and trypanocidal activities of the synthesized boronic acids were also evaluated, and it was discovered that the introduction of the boronic acid functionality improved the activity of the boronic tyrphostins. In silico target fishing with the use of a chemogenomic approach suggested that tyrosine‐phosphorylation‐regulated kinase 1a (DYRK1A) was a potential target for some of the designed compounds. On target: Boronic tyrphostins were prepared and evaluated with respect to their anticancer (IC50=0.14 μm, GH3 tumor cells) and trypanocidal activities (EC50=0.795 μm, Y strain). Results of in silico studies suggest that tyrosine‐phosphorylation‐regulated kinase 1a (DYRK1A) is a possible target in cancer‐cell lines.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.201800206