Details

Autor(en) / Beteiligte

• Hu, Xiao-Long
• Lin, Jun
• Lv, Xian-Yu
• Feng, Jia-Hao
• Zhang, Xiao-Qi
• Wang, Hao
• Ye, Wen-Cai

Titel

Synthesis and biological evaluation of clovamide analogues as potent anti-neuroinflammatory agents in vitro and in vivo

Ist Teil von

• European journal of medicinal chemistry, 2018-05, Vol.151, p.261-271

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• A series of clovamide analogues, namely, 1a–13a and 1b–13b, was synthesized and evaluated for their anti-neuroinflammatory activities using BV-2 microglia cells. Among these compounds, six (1b, 4b–8b) showed NO inhibition with no or weak cytotoxicity (CC50 > 100 μM), especially 4b, and showed an IC50 value of 2.67 μM. Enzyme activity and docking assay revealed that the six compounds, especially 4b, target inducible NO synthase (iNOS) and exhibit potent inhibitory effects on iNOS with IC50 values ranging from 1.01 μM to 29.23 μM 4b significantly suppressed the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated cells. Notably, the oral administration of 4b remarkably improved dyskinesia, reduced the expression of glial fibrillary acidic protein (GFAP)-a marker of neuroinflammation, and increased tyrosine hydroxylase-positive cells in 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine-induced Parkinson's disease (PD) mouse models. These observations demonstrated that 4b is an effective and promising candidate for PD therapy. [Display omitted] •Twenty-six clovamide analogues were synthesized.•These clovamide analogues exhibited neuroinflammation in vitro.•Compounds 4b exhibited remarkable inhibitory effects on NO production and iNOS activity.•Compounds 4b could improve the symptoms in a model of Parkinson's disease.