2. Academic Validation
  3. Synthesis, antioxidant and antichagasic properties of a selected series of hydroxy-3-arylcoumarins

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

  • Bioorg Med Chem. 2017 Jan 15;25(2):621-632. doi: 10.1016/j.bmc.2016.11.033.
Natalia Robledo-O'Ryan 1,  Maria João Matos 2,  Saleta Vazquez-Rodriguez 3,  Lourdes Santana 3,  Eugenio Uriarte 3,  Mauricio Moncada-Basualto 4,  Francisco Mura 1,  Michel Lapier 5,  Juan Diego Maya 5,  Claudio Olea-Azar 6
Affiliations

Affiliations

  • 1 Free Radical and Antioxidants Laboratory, Inorganic and Analytical Department, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone Polhammer 1007, Independencia, Santiago, Chile.
  • 2 Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: mariacmatos@gmail.com.
  • 3 Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
  • 4 Free Radical and Antioxidants Laboratory, Inorganic and Analytical Department, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone Polhammer 1007, Independencia, Santiago, Chile; Department of Environmental Sciences, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile.
  • 5 Department of Molecular Pharmacology and Clinical, Faculty of Medicine, University of Chile, Santiago, Chile.
  • 6 Free Radical and Antioxidants Laboratory, Inorganic and Analytical Department, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone Polhammer 1007, Independencia, Santiago, Chile. Electronic address: colea@uchile.cl.
PMID: 27908757 DOI: 10.1016/j.bmc.2016.11.033
Abstract

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.

Keywords

Antioxidant activity; Chagas disease; Hydroxy-3-arylcoumarins; Trypanosome.

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