NO-donor thiacarbocyanines as multifunctional agents for Alzheimer's disease.
Bioorg Med Chem
; 23(15): 4688-4698, 2015 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-26078011
ABSTRACT
Some symmetrical and unsymmetrical thiacarbocyanines bearing NO-donor nitrooxy and furoxan moieties were synthesized and studied as candidate anti-Alzheimer's drugs. All products activated soluble guanylate cyclase (sGC) in a dose-dependent manner, depending on the presence in their structures of NO-donor groups. None displayed toxicity when tested at concentrations below 10 µM on human brain microvascular endothelial cells (hCMEC/D3). Some products were capable of inhibiting amyloid ß-protein (Aß) aggregation, with a potency in the low µM concentration range, and of inhibiting aggregation of human recombinant tau protein in amyloid fibrils when incubated with the protein at 1 µM concentration. Nitrooxy derivative 21 and furoxan derivative 22 were selected to investigate synaptic plasticity. Both products, tested at 2 µM concentration, counteracted the inhibition of long-term potentiation (LTP) induced by Aß42 in hippocampal brain slices.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Carbocianinas
/
Donantes de Óxido Nítrico
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Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article