RT Journal Article
T1 Neuroprotective Action of Multitarget 7-Aminophenanthridin-6(5H)-one Derivatives against Metal-Induced Cell Death and Oxidative Stress in SN56 Cells
A1 Moyano-Cires Ivanoff, Paula Viviana
A1 Vicente Zurdo, David
A1 Blázquez-Barbadillo, Cristina
A1 Menéndez Ramos, José Carlos
A1 González Matilla, Juan Francisco
A1 Rosales Conrado, Noelia
A1 Pino Sans, Javier Del
AB Neurodegenerative diseases have been associated with brain metal accumulation, which produces oxidative stress (OS), matrix metalloproteinases (MMPs) induction, and neuronal cell death. Several metals have been reported to downregulate both the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the antioxidant enzymes regulated by it, mediating OS induction and neurodegeneration. Among a recently discovered family of multitarget 7-amino-phenanthridin-6-one derivatives (APH) the most promising compounds were tested against metal-induced cell death and OS in SN56 cells. These compounds, designed to have chelating activity, are known to inhibit some MMPs and to present antioxidant and neuroprotective effects against hydrogen peroxide treatment to SN56 neuronal cells. However, the mechanisms that mediate this protective effect are not fully understood. The obtained results show that compounds APH1, APH2, APH3, APH4, and APH5 were only able to chelate iron and copper ions among all metals studied and that APH3, APH4, and APH5 were also able to chelate mercury ion. However, none of them was able to chelate zinc, cadmium, and aluminum, thus exhibiting selective chelating activity that can be partly responsible for their neuroprotective action. Otherwise, our results indicate that their antioxidant effect is mediated through induction of the Nrf2 pathway that leads to overexpression of antioxidant enzymes. Finally, these compounds exhibited neuroprotective effects, reversing partially or completely the cytotoxic effects induced by the metals studied depending on the compound used. APH4 was the most effective and safe compound.
PB ACS Publications
SN 1948-7193
YR 2021
FD 2021-08-30
LK https://hdl.handle.net/20.500.14352/4597
UL https://hdl.handle.net/20.500.14352/4597
LA eng
NO CRUE-CSIC (Acuerdos Transformativos 2021)
NO Ministerio de Ciencia e Innovación (MICINN)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 10 abr 2025