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Dammarane triterpenes targeting α-synuclein: biological activity and evaluation of binding sites by molecular docking
oleh: Alberto Cornejo, Julio Caballero, Mario Simirgiotis, Vanessa Torres, Luisa Sánchez, Nicolás Díaz, Marcela Guimaraes, Marcos Hernández, Carlos Areche, Sergio Alfaro, Leonardo Caballero, Francisco Melo
Format: | Article |
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Diterbitkan: | Taylor & Francis Group 2021-01-01 |
Deskripsi
Parkinson's disease (PD) is a neurodegenerative disorder that affects adult people whose treatment is palliative. Thus, we decided to test three dammarane triterpenes 1, 1a, 1b, and we determined that 1 and 1a inhibit β-aggregation through thioflavine T rather than 1b. Since compound 1 was most active, we determined the interaction between α-synuclein and 1 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 1. Also, aggregates treated with 1 do not provoke neurites' retraction in N2a cells previously induced by retinoic acid. Finally, we studied the potential sites of interaction between 1 with α-synuclein fibrils using molecular modelling. Docking experiments suggest that 1 preferably interact with the site 2 of α-synuclein through hydrogen bonds with residues Y39 and T44.