In vitro phototoxicity of dihydropyridine derivatives: a photochemical and photobiological study

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Satomi OnoueYoshiko Tsuda

Abstract

Some photosensitizing drugs can cause phototoxic skin responses even after systemic administration; therefore, avoidance of undesired side-effects is a key consideration in drug discovery and development. As a prediction tool for phototoxic risk, we previously proposed the monitoring of reactive oxygen species (ROS) generated from compounds irradiated with UVA/B, which can be effective for understanding photochemical/photobiological properties. In this investigation, we evaluated the photosensitizing properties of a novel dihydropyridine derivative, with bradykinin B(2) receptor antagonist activity (compound A) using our ROS assay and several analytical/biochemical techniques. Exposure of compound A, and several dihydropyridine-type calcium channel antagonists to simulated sunlight resulted in the significant production of singlet oxygen, superoxide, or both, which indicates their photosensitive/phototoxic potential. This is consistent with the observation that compound A under UVA/B light exposure caused significant photodegradation and even peroxidation of fatty acid, which could lead to phototoxic dermatitis. Interestingly, the addition of radical scavengers, especially GSH, MPG and BHA, could attenuate the lipid peroxidatio...Continue Reading

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Citations

Dec 24, 2013·Future Medicinal Chemistry·Giuseppina IoeleGaetano Ragno
Apr 18, 2013·Journal of Pharmaceutical Sciences·Driekus GrooffErnst Ferg
Feb 20, 2013·Journal of Photochemistry and Photobiology. B, Biology·Yoshiki SetoSatomi Onoue
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Oct 12, 2011·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Wolfgang BäumlerTim Maisch

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