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dc.contributor.authorRauhamaki, Sanna
dc.contributor.authorPostila, Pekka A
dc.contributor.authorNiinivehmas, Sanna
dc.contributor.authorKortet, Sami
dc.contributor.authorSchildt, Emmi
dc.contributor.authorPasanen, Mira
dc.contributor.authorManivannan, Elangovan
dc.contributor.authorAhinko, Mira
dc.contributor.authorKoskimies, Pasi
dc.contributor.authorNyberg, Niina
dc.contributor.authorHuuskonen, Pasi
dc.contributor.authorMultamaki, Elina
dc.contributor.authorPasanen, Markku
dc.contributor.authorJuvonen, Risto O
dc.contributor.authorRaunio, Hannu
dc.contributor.authorHuuskonen, Juhani
dc.contributor.authorPentikainen, Olli T
dc.date.accessioned2018-04-10T06:28:10Z
dc.date.available2018-04-10T06:28:10Z
dc.date.issued2018
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/6266
dc.description.abstractMonoamine oxidase B (MAO-B) catalyzes deamination of monoamines such as neurotransmitters dopamine and norepinephrine. Accordingly, small-molecule MAO-B inhibitors potentially alleviate the symptoms of dopamine-linked neuropathologies such as depression or Parkinson's disease. Coumarin with a functionalized 3-phenyl ring system is a promising scaffold for building potent MAO-B inhibitors. Here, a vast set of 3-phenylcoumarin derivatives was designed using virtual combinatorial chemistry or rationally de novo and synthesized using microwave chemistry. The derivatives inhibited the MAO-B at 100 nM−1 μM. The IC50 value of the most potent derivative 1 was 56 nM. A docking-based structure-activity relationship analysis summarizes the atom-level determinants of the MAO-B inhibition by the derivatives. Finally, the cross-reactivity of the derivatives was tested against monoamine oxidase A and a specific subset of enzymes linked to estradiol metabolism, known to have coumarin-based inhibitors. Overall, the results indicate that the 3-phenylcoumarins, especially derivative 1, present unique pharmacological features worth considering in future drug development.
dc.language.isoEN
dc.publisherFrontiers Media SA
dc.relation.ispartofseriesFrontiers in chemistry
dc.relation.urihttp://dx.doi.org/10.3389/fchem.2018.00041
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/
dc.subject3-phenylcoumarin
dc.subjectmonoamine oxidase B (MAO-B)
dc.subjectstructure-activity relationship (SAR)
dc.subjectvirtual drug design
dc.subjectParkinson’s disease
dc.titleStructure-Activity Relationship Analysis of 3-Phenylcoumarin-Based Monoamine Oxidase B Inhibitors
dc.description.versionpublished version
dc.contributor.departmentSchool of Pharmacy, Activities
uef.solecris.id53357535en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© Authors
dc.relation.doi10.3389/fchem.2018.00041
dc.description.reviewstatuspeerReviewed
dc.relation.articlenumber41
dc.relation.issn2296-2646
dc.relation.volume6
dc.rights.accesslevelopenAccess
dc.type.okmA1
uef.solecris.openaccessOpen access -julkaisukanavassa ilmestynyt julkaisu


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