title: ITH12410/SC058: a new neuroprotective compound with potential in the treatment of Alzheimer's disease.
abstract: The neuroprotective profile of the dibenzothiadiazepine ITH12410/SC058 (2-chloro-5,6-dihydro-5,6-diacetyldibenzo[b,f][1,4,5]thiadiazepine) against several neurotoxicity models related to neurodegenerative diseases is herein described. ITH12410/SC058 protected SH-SY5Y cells against the loss of cell viability elicited by amyloid beta peptide and okadaic acid, a selective inhibitor of phosphoprotein phosphatase 2A that induces neurofibrillary tangle formation. Furthermore, ITH12410/SC058 is neuroprotective against several in vitro models of oxidative stress, that is, H2O2 exposure or incubation with rotenone plus oligomycin A in SH-SY5Y cells, and oxygen and glucose deprivation followed by reoxygenation in rat hippocampal slices. By contrast, ITH12410/SC058 was unable to significantly protect SH-SY5Y neuroblastoma cells against the toxicity elicited by Ca(2+) overload. Our results confirm the hypothesis that the dibenzothiadiazepine ITH12410/SC058 features its neuroprotective actions in a multitarget fashion, and is a promising drug for the treatment of neurodegenerative diseases.
authors.affiliation: Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid , C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Romero
authors.forename: Javier
authors.initials: J
authors.lastname: Egea
authors.forename: Gema C
authors.initials: GC
authors.lastname: González-Muñoz
authors.forename: Ma Dolores
authors.initials: MD
authors.lastname: Martín de Saavedra
authors.forename: Laura
authors.initials: L
authors.lastname: del Barrio
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Rodríguez-Franco
authors.forename: Santiago
authors.initials: S
authors.lastname: Conde
authors.forename: Manuela G
authors.initials: MG
authors.lastname: López
authors.forename: Mercedes
authors.initials: M
authors.lastname: Villarroya
authors.forename: Cristóbal
authors.initials: C
authors.lastname: de los Ríos
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D003987:Dibenzothiazepines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: C000597958:2-chloro-5,6-dihydro-5,6-diacetyldibenzo(b,f)(1,4,5)thiadiazepine; D003987:Dibenzothiazepines; D018696:Neuroprotective Agents
keywords: Alzheimer’s disease; Dibenzothiadiazepine; amyloid beta; neurodegenerative diseases; neurofibrillary tangles; neuroprotective drugs; oxidative stress