Evaluation of the cellular protection by novel spiropyrazole compounds in dopaminergic cell death

Eur J Med Chem. 2021 Mar 5:213:113140. doi: 10.1016/j.ejmech.2020.113140. Epub 2021 Jan 6.

Abstract

The loss of neurons is strongly correlated with aging and aging-associated disorders. In this study, cell viability assays and mitochondrial function were performed to evaluate the effect of new spiro-pyrazole derivatives, prepared from aldehydes and 3-amino-1-phenyl-2-pyrazolin-5-one, on neuroprotection in an in vitro model of dopaminergic cell death induced by 1-methyl-4-phenylpyridinium (MPP+). The percentages of neuroprotection by derivatives were found between 21.26% and 52.67% at selected concentrations (10-50 μM) with compound 4d exerting the best neuroprotective effect. The results show that the studied spiropyrazolones perform important roles in dopaminergic neuroprotection and can be used for potential new therapies in the treatment of neurodegenerative disorders including Parkinson's disease.

Keywords: Knoevenagel condensation; Michael addition; Neurodegeneration; Spiropyrazole.

MeSH terms

  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cytoprotection / drug effects
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Neuroprotective Agents
  • Pyrazoles
  • Spiro Compounds
  • pyrazole