Title:Structurally Related Edaravone Analogues: Synthesis, Antiradical, Antioxidant, and Copper-Chelating Properties
Volume: 18
Issue: 10
Author(s): Alexandre LeBlanc, Miroslava Cuperlovic-Culf, Pier Jr. Morin and Mohamed Touaibia*
Affiliation:
- Department of Chemistry and Biochemistry, Université de Moncton, Moncton, New Brunswick, NB,Canada
Keywords:
Amyotrophic lateral sclerosis, edaravone, antioxidant properties, radical scavenging abilities, copper-chelating
assay.
Abstract: Background: The current therapeutic options available to patients diagnosed with Amyotrophic
Lateral Sclerosis (ALS) are limited and edaravone is a compound that has gained significant
interest for its therapeutic potential in this condition.
Objectives: The current work was thus undertaken to synthesize and characterize a series of edaravone
analogues.
Methods: A total of 17 analogues were synthesized and characterized for their antioxidant properties,
radical scavenging potential and copper-chelating capabilities.
Results: Radical scavenging and copper-chelating properties were notably observed for edaravone.
Analogues bearing hydrogen in position 1 and a phenyl at position 3 and a phenyl in both positions of
pyrazol-5 (4H)-one displayed substantial radical scavenging, antioxidants and copper-chelating properties.
High accessibility of electronegative groups combined with higher electronegativity and partial
charge of the carbonyl moiety in edaravone might explain the observed difference in the activity of
edaravone relative to the closely related analogues 6 and 7 bearing hydrogen at position 1 and a phenyl
at position 3 (6) and a phenyl in both positions (7).
Conclusion: Overall, this study reveals a subset of edaravone analogues with interesting properties.
Further investigation of these compounds is foreseen in relevant models of oxidative stress-associated
diseases in order to assess their therapeutic potential in such conditions.
