Antioxidant activity of 4-methylcoumarins

Jens Z. Pedersen, Cristina Oliveira, Sandra Incerpi, Vineet Kumar, Anna Maria Fiore, Paolo De Vito, Ashok K. Prasad, Sanjay V. Malhotra, Virinder S. Parmar, Luciano Saso

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Polyphenols coumarins are known to act as antioxidants in biological systems, but it is difficult to distinguish their antioxidant activity from the many other effects they produce in cells. We have determined the radical scavenging capacity of 22 structurally related natural and synthetic 4-methylcoumarins, by measuring their reaction with radicals, galvinoxyl and 2,2-diphenyl-1-picrylhydrazyl, using electron paramagnetic resonance spectroscopy. Efficient antioxidant activity of 4-methylcoumarins in cells was verified using the DCF fluorescent probe assay for determination of intracellular reactive oxygen species levels. As expected, the o-dihydroxysubstituted coumarins were found to be excellent radical scavengers and better than the m-dihydroxysubstituted or monohydroxysubstituted analogues, but surprisingly the corresponding o-diacetoxy derivatives also turned out to be good scavengers, even in the absence of an esterase. Another unexpected result was that the antioxidant efficiency of 4-methylcoumarins could be modulated by introducing an ethoxycarbonylethyl substituent at the C-3 position; this effect cannot be explained by simple electron donating/withdrawing properties. Coumarin concentrations of 10 μM or less were used in all experiments, corresponding to the levels relevant for therapeutic purposes. Considering that 4-methylcoumarins, in contrast to many other coumarins, are not metabolized to toxic epoxide intermediates, these results indicate promising new strategies for the design of non-toxic antioxidant coumarin-based drugs.

Original languageEnglish (US)
Pages (from-to)1721-1728
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume59
Issue number12
DOIs
StatePublished - Dec 2007
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Antioxidant activity of 4-methylcoumarins'. Together they form a unique fingerprint.

Cite this