Phototransformations of pitavastatin - The inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase
| Autor: | Tomasz Pedzinski, Dorota Jarmużek, Marcin Hoffmann, Donata Pluskota-Karwatka, Tomasz Siodła |
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| Rok vydání: | 2020 |
| Předmět: |
Singlet oxygen
General Chemical Engineering 3 hydroxy 3 methylglutaryl coenzyme a reductase General Physics and Astronomy Quantum yield 02 engineering and technology General Chemistry Reductase urologic and male genital diseases 010402 general chemistry 021001 nanoscience & nanotechnology Photochemistry 01 natural sciences Fluorescence 0104 chemical sciences chemistry.chemical_compound Intersystem crossing chemistry medicine 0210 nano-technology Photodegradation Pitavastatin therapeutics neoplasms medicine.drug |
| Zdroj: | Journal of Photochemistry and Photobiology A: Chemistry. 389:112243 |
| ISSN: | 1010-6030 |
| DOI: | 10.1016/j.jphotochem.2019.112243 |
| Popis: | Pitavastatin (PTV) - an important cholesterol-lowering drug, is one of the most potent inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the key enzyme in cholesterol biosynthesis. PTV is sensitive to light, and upon exposure to radiation from the UVA and UVC regions undergoes partial decomposition forming photoproducts. In this study both experimental and theoretical methods were used to get insight into photophysical and photochemical properties of PTV with respect to its primary photochemistry. The PTV photodegradation quantum yield value was determined to be Ф = 0.011 (±0.002). PTV was found to undergo an intersystem crossing, however 3PTV* was formed with a low efficiency due partially to fluorescent properties exhibited by the statin. The lifetime of the excited singlet 1PTV* was calculated to be about 130 (±20) ps. 3PTV* was shown to be not involved in the formation of PTV primary photoproduct. Both PTV and its primary photoproduct were found to be able to generate singlet oxygen. Two different structures of PTV primary photoproduct were assumed to be possible on the basis of experimental measurements and quantum chemical modelling. The study provides mechanistic explanations of the both structures formation. The obtained results address to the lack of data existing till now in the scientific literature with regard to PTV phototransformations, are of great importance for safety of patients who require therapy with the statin, and should be taken into account in studies of the drug’s side effects. |
| Databáze: | OpenAIRE |
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