2. Academic Validation
  3. The p53 stabilizing agent CP-31398 and multi-kinase inhibitors. Designing, synthesizing and screening of styrylquinazoline series

The p53 stabilizing agent CP-31398 and multi-kinase inhibitors. Designing, synthesizing and screening of styrylquinazoline series

  • Eur J Med Chem. 2019 Feb 1:163:610-625. doi: 10.1016/j.ejmech.2018.12.012.
Jacek Mularski 1,  Katarzyna Malarz 2,  Marcin Pacholczyk 3,  Robert Musiol 4
Affiliations

Affiliations

  • 1 Institute of Chemistry, University of Silesia in Katowice, 75 Pułku Piechoty 1A, 41-500, Chorzów, Poland.
  • 2 A. Chelkowski Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1, 41-500, Chorzów, Poland; Silesian Center for Education and Interdisciplinary Research, University of Silesia in Katowice, 75 Pułku Piechoty 1A, 41-500, Chorzów, Poland.
  • 3 Institute of Automatic Control, Silesian University of Technology, Akademicka 16, 44-100, Gliwice, Poland.
  • 4 Institute of Chemistry, University of Silesia in Katowice, 75 Pułku Piechoty 1A, 41-500, Chorzów, Poland. Electronic address: robert.musiol@us.edu.pl.
PMID: 30562697 DOI: 10.1016/j.ejmech.2018.12.012
Abstract

Quinazoline derivatives constitute a large family of small-molecule inhibitors of tyrosine kinases. In the current study, the p53 protein reactivator CP-31398 was tested against a panel of kinases on the assumption that it was structurally similar to Other active inhibitors. Although it was found to be active in the enzyme-based assay, this compound did not block the proliferation of Cancer cells at a feasible concentration level. The styrylquinazoline was used to design new structures that might be potential multitarget inhibitors. Subsequently, a series of compounds was obtained and characterized. Their inhibitory activity in a panel of tyrosine kinases had an antiproliferative effect against several Cancer cell lines that have different expression levels of those proteins. The mode of protein interaction was tested for the most active compound in docking experiments.

Keywords

CP-31398; Kinase inhibitor; Quinazoline; p53 protein.

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