Correlations between electrochemical behaviors and DNA photooxidative properties of non-steroïdal anti-inflammatory drugs and their photoproducts

Alkali-labile lesion to DNA photosensitized, via an electron transfer mechanism, by three non-steroidal anti-inflammatory drugs (NSAIDs), ketoprofen, tiaprofenic acid and naproxen and their photoproducts during drug photolysis, was investigated using 32P-end labelled synthetic oligonucleotide. These photooxidative damages were correlated with the photophysical and electrochemical properties of drugs, appearing as the photosensitizer PS. Photophysical studies provided the excited state energies of the photosensitizer while their redox potentials and the relative stabilities of the PS− radical-anions were determined by cyclic voltammetry. On the basis of these data, we have calculated the Gibbs energy of photoinduced electron-transfer and evaluated the exergonicity of the oxidative photodamage. Moreover, kinetic control may be invoked according to the stabilities of PS−. Applied to this NSAIDs family, the photoxidative damages through electron transfer mechanism were analyzed and a good correlation with photoredox and photobiological properties was established.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► NSAIDs photoproducts lead to DNA alkali-labile lesion. ► Photophysical studies give the excited state energies of the NSAIDs photoproducts. ► Electrochemical analysis provides their redox potentials. ► The exergonicity of the photooxidative reaction is demonstrated. ► Correlation between photoredox and photobiological properties is established.