Neuroprotective Action of Multitarget 7-Aminophenanthridin-6(<i>5H</i>)-one Derivatives against Metal-Induced Cell Death and Oxidative Stress in SN56 Cells

Neurodegenerative diseases have been associated with brain metal accumulation, which produces oxidative stress (OS), matrix metalloproteinases (MMPs) induction, and neuronal cell death. Several metals reported to downregulate both the nuclear factor erythroid 2-related 2 (Nrf2) pathway antioxidant enzymes regulated by it, mediating OS induction neurodegeneration. Among a recently discovered family of multitarget 7-amino-phenanthridin-6-one derivatives (APH) most promising compounds were tested against metal-induced death in SN56 cells. These compounds, designed chelating activity, are known inhibit some MMPs present neuroprotective effects hydrogen peroxide treatment However, mechanisms that mediate this protective effect not fully understood. The obtained results show APH1, APH2, APH3, APH4, APH5 only able chelate iron copper ions among all studied also mercury ion. none them was zinc, cadmium, aluminum, thus exhibiting selective activity can be partly responsible for their action. Otherwise, our indicate is mediated through Nrf2 leads overexpression enzymes. Finally, these exhibited effects, reversing partially or completely cytotoxic induced depending on compound used. APH4 effective safe compound.