Session Information
Date: Thursday, June 23, 2016
Session Title: Parkinson's disease: Clinical trials, pharmacology and treatment
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: Taking into account the background of our research group and the knowledge that MAO and ChE activity generates ROS that cause neuronal cell death, the present work provides an overview about the potential of differently substituted coumarins as multifunctional agents.
Background: MAO and ChE generate ROS that cause neuronal cell death causing neurodegeneration. Agents able to concurrently inhibit MAO, AChE and BuChE, and scavenge free radicals, represent promising multifunctional neuroprotective agents to delay or slow the progression of neurodegenerative diseases.
Methods: Inhibition of MAO-B, AChE and BuChE, scavenging of free radicals, protection of neuronal cells from the H2O2 damage, docking studies and PAMPA assays were carried out. The influence on the activity of the different nature of the substituents introduced at position 3 of the coumarins, is herein studied.
Results: In the current work, differently substituted coumarins that exert neuroprotection in vitro against H2O2 in rat cortical neurons, and antioxidant activity in a DPPH· scavenging assay, are described. Selective and reversible inhibitors of the MAO-B were identified. Slightly inhibition of ChE was also observed for some derivatives. Interestingly, substitution at position 4 with a hydroxy group abolishes the MAO-B activity but the compounds remain active in the neuroprotection model. Further evaluation of the derivatives indicates that the nature of the substitutions can modulate the neuroprotective effects. Evaluation in a PAMPA highlighted the need to further improve the blood-brain permeability of some of the compounds. However, the compounds described here adhere to Lipinski’s rule of five, suggesting that this novel scaffold has desirable properties for the development of potential drug candidates.
Conclusions: Our data suggest sustained effects for the development of small molecules based on the coumarin core as multifunctional neuroprotective agents.
To cite this abstract in AMA style:
M.J. Matos, D. Viña, F. Rodríguez-Enríquez, S. Vilar, L. Santana, E. Uriarte. Progress in the development of small molecules based on the coumarin core as multifunctional neuroprotective agents [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/progress-in-the-development-of-small-molecules-based-on-the-coumarin-core-as-multifunctional-neuroprotective-agents/. Accessed June 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/progress-in-the-development-of-small-molecules-based-on-the-coumarin-core-as-multifunctional-neuroprotective-agents/