Adamantyl- and other polycyclic cage-based conjugates of desferrioxamine B (DFOB) for treating iron-mediated toxicity in cell models of Parkinson's disease

Abstract

The death of dopaminergic neurons is a major pathological hallmark of Parkinson's disease (PD). Elevated iron within the substantia nigra of the PD brain is thought to catalyze this neuronal death through hydroxyl radical-derived oxidative damage. Removing this excess iron presents a potential therapeutic strategy for PD. Seventeen derivatives of the non-toxic iron chelator desferrioxamine B (DFOB) were prepared by the conjugation of adamantyl- (1–4, 8–12), deconstructed adamantyl units (5–7), norborna(e)ne- (13–16) or bicyclo[2.2.2]octane-based (17) ancillary fragments to the terminal amine group. The range of experimental log P values of 1–17 (log P = 0.15–2.82) was greater than water solu..