Synthesis, antioxidant and antichagasic properties of a selected series of hydroxy-3-arylcoumarins

[Display omitted] Oxidative stress is involved in several parasitic diseases such as Chagas. Agents able to selectively modulate biochemical processes involved in the disease represent promising multifunctional agents for the delay or abolishment of the progression of this pathology. In the current...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2017-01, Vol.25 (2), p.621-632
Main Authors: Robledo-O’Ryan, Natalia, Matos, Maria João, Vazquez-Rodriguez, Saleta, Santana, Lourdes, Uriarte, Eugenio, Moncada-Basualto, Mauricio, Mura, Francisco, Lapier, Michel, Maya, Juan Diego, Olea-Azar, Claudio
Format: Article
Language:English
Subjects:
Animals
Antioxidant activity
Antioxidants - chemical synthesis
Antioxidants - chemistry
Antioxidants - pharmacology
Cell Survival - drug effects
Cercopithecus aethiops
Chagas disease
Chagas Disease - drug therapy
Chagas Disease - parasitology
Coumarins - chemical synthesis
Coumarins - chemistry
Coumarins - pharmacology
Dose-Response Relationship, Drug
Hydroxy-3-arylcoumarins
Mice
Molecular Structure
Parasitic Sensitivity Tests
RAW 264.7 Cells
Structure-Activity Relationship
Trypanocidal Agents - chemical synthesis
Trypanocidal Agents - chemistry
Trypanocidal Agents - pharmacology
Trypanosoma cruzi - drug effects
Trypanosome
Vero Cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:[Display omitted] Oxidative stress is involved in several parasitic diseases such as Chagas. Agents able to selectively modulate biochemical processes involved in the disease represent promising multifunctional agents for the delay or abolishment of the progression of this pathology. In the current work, differently substituted hydroxy-3-arylcoumarins are described, exerting both antioxidant and trypanocidal activity. Among the compounds synthesized, compound 8 showed the most interesting profile, presenting a moderate scavenging ability for peroxyl radicals (ORAC-FL=2.23) and a high degree of selectivity towards epimastigotes stage of the parasite T. cruzi (IC50=1.31μM), higher than Nifurtimox (drug currently used for treatment of Chagas disease). Interestingly, the current study revealed that small structural changes in the hydroxy-3-arylcoumarin core allow modulating both activities, suggesting that this scaffold has desirable properties for the development of promising classes of antichagasic compounds.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2016.11.033