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dc.contributor.authorJuvonen, Risto O.
dc.contributor.authorAhinko, Mira
dc.contributor.authorHuuskonen, Juhani
dc.contributor.authorRaunio, Hannu
dc.contributor.authorPentikäinen, Olli
dc.date.accessioned2020-01-07T16:14:08Z
dc.date.available2020-01-07T16:14:08Z
dc.date.issued2019
dc.identifier.citationJuvonen, R. O., Ahinko, M., Huuskonen, J., Raunio, H., & Pentikäinen, O. (2019). Development of New Coumarin-Based Profluorescent Substrates for Human Cytochrome P450 Enzymes. <i>Xenobiotica</i>, <i>49</i>(9), 1015-1024. <a href="https://doi.org/10.1080/00498254.2018.1530399" target="_blank">https://doi.org/10.1080/00498254.2018.1530399</a>
dc.identifier.otherCONVID_28647566
dc.identifier.otherTUTKAID_79052
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/67145
dc.description.abstract1. Cytochrome P450 (CYP) enzymes constitute an essential xenobiotic metabolizing system that regulates the elimination of lipophilic compounds from the body. Convenient and affordable assays for CYP enzymes are important for assessing these metabolic pathways. 2. In this study, 10 novel profluorescent coumarin derivatives with various substitutions at carbons 3, 6 and 7 were developed. Molecular modeling indicated that 3- phenylcoumarin offers an excellent scaffold for the development of selective substrate compounds for various human CYP forms, as they could be metabolized to fluorescent 7-hydroxycoumarin derivatives. Oxidation of profluorescent coumarin derivatives to fluorescent metabolites by 13 important human liver xenobiotic-metabolizing CYP forms was determined by enzyme kinetic assays. 3. Four of the coumarin derivatives were converted to fluorescent metabolites by CYP1 family enzymes, with 6-methoxy-3-(4-trifluoromethylphenyl)coumarin being oxidized selectively by CYP1A2 in human liver microsomes. Another set of four compounds were metabolized by CYP2A6 and CYP1 enzymes. 7-Methoxy-3-(3- methoxyphenyl)coumarin was oxidized efficiently by CYP2C19 and CYP2D6 in a nonselective fashion. 4. The advantages of the novel substrates were 1) an excellent signal-to-background ratio, 2) selectivity for CYP1 forms, and 3) convenient multiwell plate measurement, allowing for precise determination of potential inhibitors of important human hepatic forms CYP1A2, CYP2C19 and CYP2D6.fi
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherInforma Healthcare
dc.relation.ispartofseriesXenobiotica
dc.rightsIn Copyright
dc.subject.otherkumariini
dc.subject.otherdrug metabolism
dc.subject.otherCYP
dc.subject.otheroxidation
dc.subject.othercoumarin
dc.subject.otherderivative
dc.subject.otherenzyme kinetics
dc.titleDevelopment of New Coumarin-Based Profluorescent Substrates for Human Cytochrome P450 Enzymes
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202001071062
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosKemian laitosfi
dc.contributor.laitosDepartment of Biological and Environmental Scienceen
dc.contributor.laitosDepartment of Chemistryen
dc.contributor.oppiaineSolu- ja molekyylibiologiafi
dc.contributor.oppiaineNanoscience Centerfi
dc.contributor.oppiaineCell and Molecular Biologyen
dc.contributor.oppiaineNanoscience Centeren
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2020-01-07T10:15:24Z
dc.description.reviewstatuspeerReviewed
dc.format.pagerange1015-1024
dc.relation.issn0049-8254
dc.relation.numberinseries9
dc.relation.volume49
dc.type.versionacceptedVersion
dc.rights.copyright© Informa Healthcare, 2019.
dc.rights.accesslevelopenAccessfi
dc.subject.ysoentsyymit
dc.subject.ysolääkekemia
dc.subject.ysosubstraatit (kemia)
dc.subject.ysofluoresenssi
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p4769
jyx.subject.urihttp://www.yso.fi/onto/yso/p25557
jyx.subject.urihttp://www.yso.fi/onto/yso/p29521
jyx.subject.urihttp://www.yso.fi/onto/yso/p3265
dc.rights.urlhttp://rightsstatements.org/page/InC/1.0/?language=en
dc.relation.doi10.1080/00498254.2018.1530399


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