1. Academic Validation
  2. Ibuprofen and ketoprofen potentiate UVA-induced cell death by a photosensitization process

Ibuprofen and ketoprofen potentiate UVA-induced cell death by a photosensitization process

  • Sci Rep. 2017 Aug 21;7(1):8885. doi: 10.1038/s41598-017-09406-8.
Emmanuelle Bignon 1 2 Marco Marazzi 3 4 Vanessa Besancenot 5 6 Hugo Gattuso 3 4 Guillaume Drouot 5 6 Christophe Morell 1 Leif A Eriksson 7 Stephanie Grandemange 8 9 Elise Dumont 10 Antonio Monari 11 12
Affiliations

Affiliations

  • 1 Institut des Sciences Analytiques, UMR 5280, Université de Lyon1 (UCBL) CNRS, ENS Lyon, Lyon, France.
  • 2 Université de Lyon, ENS de Lyon, CNRS, Université Lyon 1, Laboratoire de Chimie UMR 5182, F69342, Lyon, France.
  • 3 Theory-Modeling-Simulation, Université de Lorraine - Nancy, SRSMC, Boulevard des Aiguillettes, Vandoeuvre-lès-Nancy, Nancy, France.
  • 4 Theory-Modeling-Simulation, CNRS, SRSMC, Boulevard des Aiguillettes, Vandoeuvre-lès-Nancy, Nancy, France.
  • 5 CRAN, UMR 7039 Université de Lorraine-Nancy, Vandoeuvre-lès-Nancy, Nancy, France.
  • 6 CRAN, UMR 7039 CNRS, Vandoeuvre-lès-Nancy, Nancy, France.
  • 7 Department of Chemistry & Molecular Biology, University of Gothenburg, Medicinaregatan 9 c, 40530, Göteborg, Sweden.
  • 8 CRAN, UMR 7039 Université de Lorraine-Nancy, Vandoeuvre-lès-Nancy, Nancy, France. stephanie.grandemange@univ-lorraine.fr.
  • 9 CRAN, UMR 7039 CNRS, Vandoeuvre-lès-Nancy, Nancy, France. stephanie.grandemange@univ-lorraine.fr.
  • 10 Université de Lyon, ENS de Lyon, CNRS, Université Lyon 1, Laboratoire de Chimie UMR 5182, F69342, Lyon, France. elise.dumont@ens-lyon.fr.
  • 11 Theory-Modeling-Simulation, Université de Lorraine - Nancy, SRSMC, Boulevard des Aiguillettes, Vandoeuvre-lès-Nancy, Nancy, France. antonio.monari@univ-lorraine.fr.
  • 12 Theory-Modeling-Simulation, CNRS, SRSMC, Boulevard des Aiguillettes, Vandoeuvre-lès-Nancy, Nancy, France. antonio.monari@univ-lorraine.fr.
Abstract

Nonsteroidal 2-arylproprionic acids are widely used, over-the-counter, anti-inflammatory drugs. Photosensitivity is a commonly overlooked adverse effect of these drugs. Based on the combined use of cell viability assays and molecular modeling, we prove and rationalize the photochemical pathways triggering photosensitization for two drugs, ibuprofen and ketoprofen. As its parent compound benzophenone, ketoprofen produces singlet oxygen, upon triplet manifold population. However, ibuprofen and ketoprofen photodissociate and hence may generate two highly reactive radicals. The formation of metastable aggregates between the two drugs and B-DNA is also directly probed by molecular dynamics. Our approach characterizes the coupled influence of the drug's intrinsic photochemistry and the interaction pattern with DNA. The photosensitization activity of nonsteroidal 2-arylproprionic acids, being added to gels and creams for topical use, should be crucially analyzed and rationalized to enact the proper preventive measures.

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