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dc.contributor.authorNiinivehmas, S
dc.contributor.authorPostila, PA
dc.contributor.authorRauhamäki, S
dc.contributor.authorManivannan, E
dc.contributor.authorKortet, S
dc.contributor.authorAhinko, M
dc.contributor.authorHuuskonen, P
dc.contributor.authorNyberg, N
dc.contributor.authorKoskimies, P
dc.contributor.authorLätti, S
dc.contributor.authorMultamäki, E
dc.contributor.authorJuvonen, RO
dc.contributor.authorRaunio, H
dc.contributor.authorPasanen, M
dc.contributor.authorHuuskonen, J
dc.contributor.authorPentikäinen, OT
dc.date.accessioned2018-05-24T10:16:43Z
dc.date.available2018-05-24T10:16:43Z
dc.date.issued2018
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/6655
dc.description.abstractA comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-β-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced ≥62% HSD1 inhibition at 5 µM and, furthermore, three of them produced ≥68% inhibition at 1 µM. 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-β-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.isoenglanti
dc.publisherInforma UK Limited
dc.relation.ispartofseriesJournal of Enzyme Inhibition and Medicinal Chemistry
dc.relation.urihttp://dx.doi.org/10.1080/14756366.2018.1452919
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/
dc.subject3-Phenylcoumarin
dc.subject17-β-hydroxysteroid dehydrogenase 1 (HSD1)
dc.subject3-imidazolecoumarin
dc.subjectaromatase
dc.subjectstructure-activity relationship (SAR)
dc.titleBlocking oestradiol synthesis pathways with potent and selective coumarin derivatives
dc.description.versionpublished version
dc.contributor.departmentSchool of Pharmacy, Activities
dc.contributor.departmentA.I. Virtanen -instituutti
uef.solecris.id53730906en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© Authors
dc.relation.doi10.1080/14756366.2018.1452919
dc.description.reviewstatuspeerReviewed
dc.format.pagerange743-754
dc.relation.issn1475-6366
dc.relation.issue1
dc.relation.volume33
dc.rights.accesslevelopenAccess
dc.type.okmA1
uef.solecris.openaccessEi


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