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

Konstantin Chegaev, Antonella Federico, Elisabetta Marini, Barbara Rolando, Roberta Fruttero, Michela Morbin, Giacomina Rossi, Valeria Fugnanesi, Antonio Bastone, Mario Salmona, Nahuai B. Badiola, Laura Gasparini, Sara Cocco, Cristian Ripoli, Claudio Grassi, Alberto Gasco

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4688-4698
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number15
DOIs
Publication statusPublished - Jul 23 2015

Keywords

  • Alzheimer disease
  • Long term potentiation
  • Nitric oxide
  • Tau proteins
  • Thiacarbocyanines
  • β-Amyloid

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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  • Cite this

    Chegaev, K., Federico, A., Marini, E., Rolando, B., Fruttero, R., Morbin, M., Rossi, G., Fugnanesi, V., Bastone, A., Salmona, M., Badiola, N. B., Gasparini, L., Cocco, S., Ripoli, C., Grassi, C., & Gasco, A. (2015). NO-donor thiacarbocyanines as multifunctional agents for Alzheimer's disease. Bioorganic and Medicinal Chemistry, 23(15), 4688-4698. https://doi.org/10.1016/j.bmc.2015.05.050