Dammarane triterpenes targeting α-synuclein: biological activity and evaluation of binding sites by molecular docking.

Parkinson's disease (PD) is a neurodegenerative disorder that affects adult people whose treatment is palliative. Thus, we decided to test three dammarane triterpenes , , , and we determined that and inhibit β-aggregation through thioflavine T rather than . Since compound was most active, we determined the interaction between α-synuclein and at 50 µM (Kd) through microscale thermophoresis. Also, we observed differences in height and diameter of aggregates, and α-synuclein remains unfolded in the presence of . Also, aggregates treated with do not provoke neurites' retraction in N2a cells previously induced by retinoic acid. Finally, we studied the potential sites of interaction between with α-synuclein fibrils using molecular modelling. Docking experiments suggest that preferably interact with the site 2 of α-synuclein through hydrogen bonds with residues Y39 and T44.