title: NO-donor thiacarbocyanines as multifunctional agents for Alzheimer's disease.
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.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Chegaev
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Marini
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rolando
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via Pietro Giuria 9, 10125 Torino, Italy. Electronic address: roberta.fruttero@unito.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fruttero
authors.affiliation: Division of Neurology V and Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Morbin
authors.affiliation: Division of Neurology V and Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Giacomina
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Division of Neurology V and Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Fugnanesi
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milano, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bastone
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Nahuai B
authors.initials: NB
authors.lastname: Badiola
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Gasparini
authors.affiliation: Institute of Human Physiology, UniversitàCattolica, Roma, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cocco
authors.affiliation: Institute of Human Physiology, UniversitàCattolica, Roma, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Ripoli
authors.affiliation: Institute of Human Physiology, UniversitàCattolica, Roma, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Grassi
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gasco
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D002232:Carbocyanines / Q000627:therapeutic use*; D006801:Humans; D020030:Nitric Oxide Donors / Q000627:therapeutic use*
chemical_list: D002232:Carbocyanines; D020030:Nitric Oxide Donors
keywords: Alzheimer disease; Long term potentiation; Nitric oxide; Tau proteins; Thiacarbocyanines; β-Amyloid