α-Synuclein inhibitor 8 effectively impedes α-Synuclein aggregation and disaggregation with an IC50 of 2.5 µM, demonstrating substantial reduction in neuronal inclusion formation, which contributes to reparative effects in damaged neurons and symptomatic improvement in Parkinson’s disease (PD)-like models. The compound also exhibits high antioxidant activity and low cytotoxicity [1].

α-Synuclein inhibitor 8 (Compound 2ee) inhibits α-Synuclein aggregation dose-dependently (0-100 µM; 0-96 h) [1], disassembling mature fibrils into soluble proteins and some short insoluble fibers at 100 µM and 48 h [1]. It increases reactive oxygen species scavenging rate dose-dependently (1-1000 µM; 0.5 h or 24 h) and shows low cytotoxicity in H4 and SH-SY5Y cells, with viability over 80% [1]. At 10 µM for 38 h, α-Synuclein inhibitor 8 inhibits α-Synuclein aggregation and inclusion body formation in H4 cells [1].

Compound 2ee (α-Synuclein inhibitor 8), administered at a single dose of 0.9 μg/μL via intravenous injection, significantly ameliorated symptoms such as reduced grip strength, limb rigidity, and impaired balance in a Parkinson's disease (PD) C57 mouse model. Furthermore, α-Synuclein inhibitor 8 demonstrated a neuroprotective effect on the caudate putamen (CPu) and substantia nigra pars reticulata (SNr) within the brains of these Parkinson's disease C57 mouse models [1].