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

Alberto Cornejo, Julio Caballero, Mario Simirgiotis, Vanessa Torres, Luisa Sánchez, Nicolás Díaz, Marcela Guimaraes, Marcos Hernández, Carlos Areche, Sergio Alfaro, Leonardo Caballero, Francisco Melo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)154-162
Number of pages9
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume36
Issue number1
DOIs
Publication statusPublished - 2021

Keywords

  • drug target
  • natural compounds modifiers
  • oligomers
  • Parkinson’s disease

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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