Coumarin-Based Profluorescent and Fluorescent Substrates for Determining Xenobiotic-Metabolizing Enzyme Activities In Vitro
in vivo methods, such as spectrophotometric, fluorometric, mass spectrometric,<br />and radioactivity-based techniques. In fluorescence-based assays, the reaction produces a fluorescent<br />product from a nonfluorescent substrate or vice versa. Fluorescence-based enzyme assays are<br...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/13/4708 |
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| author | Hannu Raunio Olli Pentikäinen Risto O. Juvonen |
| author_facet | Hannu Raunio Olli Pentikäinen Risto O. Juvonen |
| author_sort | Hannu Raunio |
| collection | DOAJ |
| description | in vivo methods, such as spectrophotometric, fluorometric, mass spectrometric,<br />and radioactivity-based techniques. In fluorescence-based assays, the reaction produces a fluorescent<br />product from a nonfluorescent substrate or vice versa. Fluorescence-based enzyme assays are<br />usually highly sensitive and specific, allowing measurements on small specimens of tissues with<br />low enzyme activities. Fluorescence assays are also amenable to miniaturization of the reaction<br />mixtures and can thus be done in high throughput. 7-Hydroxycoumarin and its derivatives are<br />widely used as fluorophores due to their desirable photophysical properties. They possess a large -<br />conjugated system with electron-rich and charge transfer properties. This conjugated structure leads<br />to applications of 7-hydroxycoumarins as fluorescent sensors for biological activities. We describe in<br />this review historical highlights and current use of coumarins and their derivatives in evaluating<br />activities of the major types of xenobiotic-metabolizing enzyme systems. Traditionally, coumarin<br />substrates have been used to measure oxidative activities of cytochrome P450 (CYP) enzymes. For this<br />purpose, profluorescent coumarins are very sensitive, but generally lack selectivity for individual CYP<br />forms. With the aid of molecular modeling, we have recently described several new coumarin-based<br />substrates for measuring activities of CYP and conjugating enzymes with improved selectivity. |
| first_indexed | 2024-03-10T18:44:43Z |
| format | Article |
| id | doaj.art-9e4f1e575f5a4310bd61a164552d3bba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:44:43Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9e4f1e575f5a4310bd61a164552d3bba2023-11-20T05:35:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012113470810.3390/ijms21134708Coumarin-Based Profluorescent and Fluorescent Substrates for Determining Xenobiotic-Metabolizing Enzyme Activities In VitroHannu Raunio0Olli Pentikäinen1Risto O. Juvonen2School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70600 Kuopio, FinlandInstitute of Biomedicine, Faculty of Medicine, University of Turku, 20520 Turku, FinlandSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70600 Kuopio, Finlandin vivo methods, such as spectrophotometric, fluorometric, mass spectrometric,<br />and radioactivity-based techniques. In fluorescence-based assays, the reaction produces a fluorescent<br />product from a nonfluorescent substrate or vice versa. Fluorescence-based enzyme assays are<br />usually highly sensitive and specific, allowing measurements on small specimens of tissues with<br />low enzyme activities. Fluorescence assays are also amenable to miniaturization of the reaction<br />mixtures and can thus be done in high throughput. 7-Hydroxycoumarin and its derivatives are<br />widely used as fluorophores due to their desirable photophysical properties. They possess a large -<br />conjugated system with electron-rich and charge transfer properties. This conjugated structure leads<br />to applications of 7-hydroxycoumarins as fluorescent sensors for biological activities. We describe in<br />this review historical highlights and current use of coumarins and their derivatives in evaluating<br />activities of the major types of xenobiotic-metabolizing enzyme systems. Traditionally, coumarin<br />substrates have been used to measure oxidative activities of cytochrome P450 (CYP) enzymes. For this<br />purpose, profluorescent coumarins are very sensitive, but generally lack selectivity for individual CYP<br />forms. With the aid of molecular modeling, we have recently described several new coumarin-based<br />substrates for measuring activities of CYP and conjugating enzymes with improved selectivity.https://www.mdpi.com/1422-0067/21/13/4708cytochrome P450CYPglucuronidationsulfonationmethylationfluorescence |
| spellingShingle | Hannu Raunio Olli Pentikäinen Risto O. Juvonen Coumarin-Based Profluorescent and Fluorescent Substrates for Determining Xenobiotic-Metabolizing Enzyme Activities In Vitro International Journal of Molecular Sciences cytochrome P450 CYP glucuronidation sulfonation methylation fluorescence |
| title | Coumarin-Based Profluorescent and Fluorescent Substrates for Determining Xenobiotic-Metabolizing Enzyme Activities In Vitro |
| title_full | Coumarin-Based Profluorescent and Fluorescent Substrates for Determining Xenobiotic-Metabolizing Enzyme Activities In Vitro |
| title_fullStr | Coumarin-Based Profluorescent and Fluorescent Substrates for Determining Xenobiotic-Metabolizing Enzyme Activities In Vitro |
| title_full_unstemmed | Coumarin-Based Profluorescent and Fluorescent Substrates for Determining Xenobiotic-Metabolizing Enzyme Activities In Vitro |
| title_short | Coumarin-Based Profluorescent and Fluorescent Substrates for Determining Xenobiotic-Metabolizing Enzyme Activities In Vitro |
| title_sort | coumarin based profluorescent and fluorescent substrates for determining xenobiotic metabolizing enzyme activities in vitro |
| topic | cytochrome P450 CYP glucuronidation sulfonation methylation fluorescence |
| url | https://www.mdpi.com/1422-0067/21/13/4708 |
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