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: Alejandro Romero, Javier Egea, Gema C González-Muñoz, Ma Dolores Martín de Saavedra, Laura del Barrio, María Isabel Rodríguez-Franco, Santiago Conde, Manuela G López, Mercedes Villarroya, Cristóbal de los Ríos
• Journal: ACS chemical neuroscience (ACS Chem Neurosci) Vol. 5 Issue 9 Pg. 770-5 (Sep 17 2014) ISSN: 1948-7193 [Electronic] United States
• PMID: 25008046 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• 2-chloro-5,6-dihydro-5,6-diacetyldibenzo(b,f)(1,4,5)thiadiazepine
• Dibenzothiazepines
• Neuroprotective Agents

Topics

• Alzheimer Disease (drug therapy)
• Animals
• Dibenzothiazepines (chemistry, pharmacology, therapeutic use)
• Humans
• Models, Biological
• Neuroprotective Agents (chemistry, therapeutic use)
• Oxidative Stress (drug effects)