NO-donor thiacarbocyanines as multifunctional agents for Alzheimer's disease. Issue 15 (1st August 2015)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 15(2015)
• Page Start: 4688
• Page End: 4698
• Publication Date: 2015-08-01
• Subjects: Alzheimer disease -- Nitric oxide -- β-Amyloid -- Tau proteins -- Thiacarbocyanines -- Long term potentiation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.05.050
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.