Design, synthesis and evaluation of multifunctional salphen derivatives for the treatment of Alzheimer's disease.
Eur J Med Chem
; 87: 540-51, 2014 Nov 24.
Article
em En
| MEDLINE
| ID: mdl-25290683
ABSTRACT
A series of salphen derivatives (1-26) have been designed, synthesized, and evaluated as chemical reagents that target and modulate multiple facets of Alzheimer's disease. Most of the compounds exhibit a significant ability to inhibit self-induced and Cu(2+)-induced ß-amyloid (Aß1-42) aggregation, and to function as potential antioxidants and biometal chelators. In particular, the antioxidant activity of compound 2 is 2.6-fold of the trolox value by using the ABTS radical scavenging method, and it also shows a significant ability to inhibit self-induced and Cu(2+)-induced ß-amyloid (Aß1-42) aggregation (70.3%, 20 µM and 85.7%, 50 µM, respectively). Moreover, it is capable of decreasing reactive oxygen species (ROS) induced by Cu(2+)-Aß, shows a good neuroprotective effect in human SH-SY5Y neuroblastoma cells and can cross the blood-brain barrier. In addition, compound 2 retains the activities of antioxidant, anti Aß aggregation and neuroprotection after capturing the metal ions Cu(2+), Fe(3+) and Zn(2+) (its metal complexes 18, 22 and 23). Taken together, these results suggest that compound 2 might be a promising lead compound for AD treatment.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenilenodiaminas
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Fármacos Neuroprotetores
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Doença de Alzheimer
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article