May 14, 2014

Synthesis and characterization of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for treatment of Alzheimer's disease

Biochimica Et Biophysica Acta
Jinggong LiuDing Li

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that is characterized by dementia, cognitive impairment, and memory loss. Diverse factors are related to the development of AD, such as increased level of β-amyloid (Aβ), acetylcholine, metal ion deregulation, hyperphosphorylated tau protein, and oxidative stress. The following methods were used: organic syntheses of 1H-phenanthro[9,10-d]imidazole derivatives, inhibition of self-mediated and metal-induced Aβ1-42 aggregation, inhibition studies for acetylcholinesterase and butyrylcholinesterase, anti-oxidation activity studies, CD, MTT assay, transmission electron microscopy, dot plot assay, gel electrophoresis, Western blot, and molecular docking studies. We synthesized and characterized a new type of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for AD treatment. Our results showed that most of these derivatives exhibited strong Aβ aggregation inhibitory activity. Compound 9g had 74% Aβ1-42 aggregation inhibitory effect at 10μM concentration with its IC50 value of 6.5μM for self-induced Aβ1-42 aggregation. This compound also showed good inhibition of metal-mediated (Cu(2+) and Fe(2+)) and acetylcholinesterase-induced Aβ1-42 aggreg...Continue Reading

  • References51
  • Citations6

Citations

Mentioned in this Paper

Familial Alzheimer Disease (FAD)
Memory Loss
Brain Diseases
Derivatives
APP protein, human
Western Blotting
BCHE
Antioxidant Effect
Aggregation
Imidazole derivatives, antimycotic for systemic use

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