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 in a dose-dependent manner (0-100 µM; 0-96 h) [1]. At a concentration of 100 µM and exposure time of 48 h, it disassembles mature fibrils into soluble proteins and a small amount of short insoluble fibers [1]. Additionally, α-Synuclein inhibitor 8 increases the rate of reactive oxygen species scavenging dose-dependently (1-1000 µM; 0.5 h or 24 h). It exhibits low cytotoxicity in H4 and SH-SY5Y cells, with cell viability exceeding 80% [1]. At 10 µM for 38 h, α-Synuclein inhibitor 8 shows inhibitory effects on the formation of α-Synuclein aggregation and inclusion bodies within 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].