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 β-protein (Aβ) 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 Aβ42 in hippocampal brain slices.

NO-donor thiacarbocyanines as multifunctional agents for Alzheimer’s disease

CHEGAEV, Konstantin;FEDERICO, ANTONELLA;MARINI, Elisabetta;ROLANDO, Barbara;FRUTTERO, Roberta;GASCO, Alberto
2015

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 β-protein (Aβ) 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 Aβ42 in hippocampal brain slices.
BIOORGANIC & MEDICINAL CHEMISTRY
23
15
4688
4698
http://www.sciencedirect.com/science/article/pii/S0968089615004721
Alzheimer disease, Nitric oxide, β-Amyloid, Tau proteins, Thiacarbocyanines, Long term potentiation
Chegaev, Konstantin; Federico, Antonella; Marini, Elisabetta; Rolando, Barbara; Fruttero, Roberta; Morbin, Michela; Rossi, Giacomina; Fugnanesi, Valeria; Bastone, Antonio; Salmona, Mario; Badiola, Nahuai B.; Gasparini, Laura; Cocco, Sara; Ripoli, Cristian; Grassi, Claudio; Gasco, Alberto
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1522113
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