Synthesis and evaluation of new pyridyl/pyrazinyl thiourea derivatives: Neuroprotection against amyloid-ß-induced toxicity.
Eur J Med Chem
; 141: 322-334, 2017 Dec 01.
Article
in En
| MEDLINE
| ID: mdl-29031076
ABSTRACT
Herein, we report synthesis and evaluation of new twenty six small molecules against ß amyloid (Aß)-induced opening of mitochondrial permeability transition pore (mPTP) using JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The neuroprotective effect of seventeen compounds against Aß-induced mPTP opening was superior to that of the standard Cyclosporin A (CsA). Fifteen derivatives eliciting increased green to red fluorescence percentage less than 40.0% were evaluated for their impact on ATP production, cell viability and neuroprotection against Aß-induced neuronal cell death. Among evaluated compounds, derivatives 9w, 9r and 9k had safe profile regarding ATP production and cell viability. In addition, they exhibited significant neuroprotection (69.3, 51.8 and 48.2% respectively). Molecular modeling study using CDocker algorithm predicted plausible binding modes explaining the elicited mPTP blocking activity. Hence, this study suggests compounds 9w, 9r and 9k as leads for further development of novel therapy to Alzheimer's disease.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Thiourea
/
Amyloid beta-Peptides
/
Neuroprotective Agents
/
Small Molecule Libraries
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Year:
2017
Type:
Article