Premium
Synthesis and Evaluation of the Anticancer and Trypanocidal Activities of Boronic Tyrphostins
Author(s) -
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
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800206
Subject(s) - boronic acid , chemistry , moiety , combinatorial chemistry , in silico , biochemistry , stereochemistry , gene
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.