2024-03-29T15:36:19Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/366762021-06-21T12:37:04Zcom_10261_81com_10261_5col_10261_334
N-Acylaminophenothiazines: neuroprotective agents displaying multifunctional activities for a potential treatment of Alzheimer’s disease
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
N-Acylaminophenothiazines
Butyrylcholinesterase inhibition
Neuroprotection
Oxidative stress
Okadaic acid
Beta-amyloid peptide
Calcium modulation
Alzheimer’s disease
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
2011-06-09T11:41:37Z
2011-06-09T11:41:37Z
2011
artículo
European Journal of Medicinal Chemistry 46 : 2224-2235 (2011)
http://hdl.handle.net/10261/36676
10.1016/j.ejmech.2011.03.003
eng
http://dx.doi.org/10.1016/j.ejmech.2011.03.003
closedAccess
Elsevier