Synthesis of new heterocyclic compounds based on pyrazolopyridine scaffold and evaluation of their neuroprotective potential in MPP+-induced neurodegeneration.

Abstract

Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease affect millions of people in the world. Thus several new approaches to treat brain disorders are under development. The aim of the present study is to synthesize potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then to evaluate their effects in MPP+-induced neurodegeneration in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in apoptosis-related proteins including bax, Bcl-2, Bcl-xl and caspase-3 were investigated by western blot technique. Based on the cell viability results obtained by MTT assay, the percentage of neuroprotection-induced by compounds against MPP+-induced neurotoxicity in SH-SY5Y cells was between 20% and 30% at 5 μM concentrations of all synthesized compounds. Moreover, the downregulation in pro-apoptotic proteins including bax and caspase-3 were found following the novel synthesized compounds treatments and these effects were observed in a dose-dependent manner. Our results provide an evidence that these heterocyclic compounds based on pyrazolopyridine derivatives may have a role on dopaminergic neuroprotection via antiapoptotic pathways.

• Authors: Jabrane Jouha, Mohammed Loubidi, Jamila Bouali, Salha Hamri, Abderrafia Hafid, Franck Suzenet, Gérald Guillaumet, Taner Dagcı, Mostafa Khouili, Fadime Aydın, Luciano Saso, Güliz Armagan
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 129 Pg. 41-52 (Mar 31 2017) ISSN: 1768-3254 [Electronic] France
• PMID: 28214632 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• Heterocyclic Compounds
• Neuroprotective Agents
• Pyrazoles
• Pyridines
• pyrazolopyridine

Topics

• Apoptosis Regulatory Proteins (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Heterocyclic Compounds (chemistry, pharmacology)
• Humans
• Neuroblastoma (pathology)
• Neurodegenerative Diseases (chemically induced, drug therapy)
• Neuroprotective Agents (chemical synthesis, pharmacology)
• Pyrazoles (chemistry, pharmacology)
• Pyridines (chemistry, pharmacology)