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dc.contributor.authorNiinivehmas, Sanna
dc.contributor.authorPostila, Pekka
dc.contributor.authorRauhamäki, Sanna
dc.contributor.authorManivannan, Elangovan
dc.contributor.authorKortet, Sami
dc.contributor.authorAhinko, Mira
dc.contributor.authorHuuskonen, Pasi
dc.contributor.authorNyberg, Niina
dc.contributor.authorKoskimies, Pasi
dc.contributor.authorLätti, Sakari
dc.contributor.authorMultamäki, Elina
dc.contributor.authorJuvonen, Risto O.
dc.contributor.authorRaunio, Hannu
dc.contributor.authorPasanen, Markku
dc.contributor.authorHuuskonen, Juhani
dc.contributor.authorPentikäinen, Olli
dc.date.accessioned2018-04-19T09:12:13Z
dc.date.available2018-04-19T09:12:13Z
dc.date.issued2018
dc.identifier.citationNiinivehmas, S., Postila, P., Rauhamäki, S., Manivannan, E., Kortet, S., Ahinko, M., Huuskonen, P., Nyberg, N., Koskimies, P., Lätti, S., Multamäki, E., Juvonen, R. O., Raunio, H., Pasanen, M., Huuskonen, J., & Pentikäinen, O. (2018). Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives. <i>Journal of Enzyme Inhibition and Medicinal Chemistry</i>, <i>33</i>(1), 743-754. <a href="https://doi.org/10.1080/14756366.2018.1452919" target="_blank">https://doi.org/10.1080/14756366.2018.1452919</a>
dc.identifier.otherCONVID_27988911
dc.identifier.otherTUTKAID_77290
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/57698
dc.description.abstractA comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-b-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced 62% HSD1 inhibition at 5 mM and, furthermore, three of them produced 68% inhibition at 1 mM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases. Most of the analogues are only modestly active with 17-b-hydroxysteroid dehydrogenase 2 – a requirement for lowering effective oestradiol levels in vivo. Moreover, the analysis led to the synthesis and discovery of 3-imidazolecoumarin as a potent aromatase inhibitor. In short, coumarin core can be tailored with specific ring and polar moiety substitutions to block either the sulphatase pathway or the aromatase pathway for treating breast cancer and endometriosis.
dc.language.isoeng
dc.publisherTaylor and Francis
dc.relation.ispartofseriesJournal of Enzyme Inhibition and Medicinal Chemistry
dc.subject.other3-Phenylcoumarin
dc.subject.other17-β-hydroxysteroid dehydrogenase 1 (HSD1)
dc.subject.other3-imidazolecoumarin
dc.subject.otherstructure-activity relationship (SAR)
dc.titleBlocking oestradiol synthesis pathways with potent and selective coumarin derivatives
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201804061945
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.oppiaineEkologia ja evoluutiobiologiafi
dc.contributor.oppiaineSolu- ja molekyylibiologiafi
dc.contributor.oppiaineOrgaaninen kemiafi
dc.contributor.oppiaineNanoscience Centerfi
dc.contributor.oppiaineEcology and Evolutionary Biologyen
dc.contributor.oppiaineCell and Molecular Biologyen
dc.contributor.oppiaineOrganic Chemistryen
dc.contributor.oppiaineNanoscience Centeren
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2018-04-06T12:15:11Z
dc.description.reviewstatuspeerReviewed
dc.format.pagerange743-754
dc.relation.issn1475-6366
dc.relation.numberinseries1
dc.relation.volume33
dc.type.versionpublishedVersion
dc.rights.copyright© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.
dc.rights.accesslevelopenAccessfi
dc.subject.ysoaromataasi
jyx.subject.urihttp://www.yso.fi/onto/yso/p38965
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.1080/14756366.2018.1452919


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© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License.
Except where otherwise noted, this item's license is described as © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.