Dammarane triterpenes targeting α-synuclein: biological activity and evaluation of binding sites by molecular docking
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Archivos
Fecha
2021
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
Taylor and Francis Ltd.
Nombre de Curso
Licencia CC
Attribution 4.0 International (CC BY 4.0)
Licencia CC
https://creativecommons.org/licenses/by/4.0/
Resumen
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.
Notas
Indexación Scopus
Palabras clave
drug target, natural compounds modifiers, oligomers, Parkinson’s disease
Citación
Journal of Enzyme Inhibition and Medicinal Chemistry Volume 36 Issue 1 Pages 154 - 1622021
DOI
10.1080/14756366.2020.1851216