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Closed Access item N-Acylaminophenothiazines: neuroprotective agents displaying multifunctional activities for a potential treatment of Alzheimer’s disease

Authors:González Muñoz, Gema C.
Arce, Mariana P.
López, Beatriz
López, Beatriz
Romero, Alejandro
del Barrio, Laura
Martín de Saavedra, María Dolores
Egea, Javier
León, Rafael
Villarroya, Mercedes
López, Manuela G.
García, Antonio G.
Conde, Santiago
Rodríguez Franco, María Isabel
Keywords:N-Acylaminophenothiazines, Butyrylcholinesterase inhibition, Neuroprotection, Oxidative stress, Okadaic acid, Beta-amyloid peptide, Calcium modulation, Alzheimer’s disease
Issue Date:2011
Citation:European Journal of Medicinal Chemistry 46 : 2224-2235 (2011)
Abstract:We have previously reported the multifunctional profile of N-(3-chloro-10H-phenothiazin-10-yl)-3- (dimethylamino)propanamide (1) as an effective neuroprotectant and selective butyrylcholinesterase inhibitor. In this paper, we have developed a series of N-acylaminophenothiazines obtained from our compound library or newly synthesised. At micro- and sub-micromolar concentrations, these compounds selectively inhibited butyrylcholinesterase (BuChE), protected neurons against damage caused by both exogenous and mitochondrial free radicals, showed low toxicity, and could penetrate into the CNS. In addition, N-(3-chloro-10H-phenothiazin-10-yl)-2-(pyrrolidin-1-yl)acetamide (11) modulated the cytosolic calcium concentration and protected human neuroblastoma cells against several toxics, such as calcium overload induced by an L-type Ca2þ-channel agonist, tau-hyperphosphorylation induced by okadaic acid and Ab peptide
Publisher version (URL):http://dx.doi.org/10.1016/j.ejmech.2011.03.003
Appears in Collections:(IQM) Artículos

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