Synthesis and Antibacterial Evaluation of New Pyrazolo[3,4- d]pyrimidines Kinase Inhibitors

Molecules. 2020 Nov 16;25(22):5354. doi: 10.3390/molecules25225354.

Abstract

Pyrazolo[3,4-d]pyrimidines represent an important class of heterocyclic compounds well-known for their anticancer activity exerted by the inhibition of eukaryotic protein kinases. Recently, pyrazolo[3,4-d]pyrimidines have become increasingly attractive for their potential antimicrobial properties. Here, we explored the activity of a library of in-house pyrazolo[3,4-d]pyrimidines, targeting human protein kinases, against Staphylococcus aureus and Escherichia coli and their interaction with ampicillin and kanamycin, representing important classes of clinically used antibiotics. Our results represent a first step towards the potential application of dual active pyrazolo[3,4-d]pyrimidine kinase inhibitors in the prevention and treatment of bacterial infections in cancer patients.

Keywords: antimicrobials; kinase inhibitors; pyrazolo[3,4-d]pyrimidines; β-lactam antibiotics.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Microbial Sensitivity Tests
  • Phylogeny
  • Protein Domains
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development

Substances

  • Anti-Bacterial Agents
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Protein Kinases