Mahmoud El Safadi

The accumulation of iron in dopaminergic neurons can cause oxidative stress and dopaminergic neuron degeneration. Iron chelation therapy may reduce dopaminergic neurodegeneration, but chelators should be targeted towards dopaminergic cells. In this work, two series of compounds based on 8-hydroxyquinoline and deferiprone, iron chelators that have amphetamine-like structures, have been designed, synthesized and characterized. Each of these compounds chelated iron ions in aqueous solution. The hydroxyquinoline-based compounds exhibited stronger iron-binding constants than those of the deferiprone derivatives. The hydroxyquinoline-based compounds also exhibited greater free radical scavenging activities compared to the deferiprone derivatives. Molecular dynamics simulations showed that the hydroxyquinoline-based compounds generally bound well within human dopamine transporter cavities. Thus, these compounds are excellent candidates for future exploration as drugs against diseases that are affected by iron-induced dopaminergic neuron damage, such as Parkinson’s disease.