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dc.contributor.authorPrismawan, Deka
dc.contributor.authorvan der Vlag, Ramon
dc.contributor.authorGuo, Hao
dc.contributor.authorDekker, Frank J
dc.contributor.authorHirsch, Anna K H
dc.date.accessioned2019-07-03T14:07:18Z
dc.date.available2019-07-03T14:07:18Z
dc.date.issued2019-05-01
dc.identifier.citationHelv Chim Acta. 2019 May;102(5):e1900040. doi: 10.1002/hlca.201900040. Epub 2019 May 2.en_US
dc.identifier.issn0018-019X
dc.identifier.pmid31231138
dc.identifier.doi10.1002/hlca.201900040
dc.identifier.urihttp://hdl.handle.net/10033/621844
dc.description.abstractHuman 15-lipoxygenase-1 (15-LOX-1) belongs to the class of lipoxygenases, which catalyze oxygenation of polyunsaturated fatty acids, such as arachidonic and linoleic acid. Recent studies have shown that 15-LOX-1 plays an important role in physiological processes linked to several diseases such as airway inflammation disease, coronary artery disease, and several types of cancer such as rectal, colon, breast and prostate cancer. In this study, we aimed to extend the structural diversity of 15-LOX-1 inhibitors, starting from the recently identified indolyl core. In order to find new scaffolds, we employed a combinatorial approach using various aromatic aldehydes and an aliphatic hydrazide tail. This scaffold-hopping study resulted in the identification of the 3-pyridylring as a suitable replacement of the indolyl core with an inhibitory activity in the micromolar range (IC50=16±6 μm) and a rapid and efficient structure-activity relationship investigation.en_US
dc.language.isoenen_US
dc.publisherWiley-Blackwellen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject15-lipoxygenase-1en_US
dc.subjectacylhydrazoneen_US
dc.subjectcombinatorial chemistryen_US
dc.subjectenzyme inhibitorsen_US
dc.subjectstructure–activity relationshipsen_US
dc.titleReplacement of an Indole Scaffold Targeting Human 15-Lipoxygenase-1 Using Combinatorial Chemistry.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalHelvetica Chimica Actaen_US
refterms.dateFOA2019-07-03T14:07:19Z
dc.source.journaltitleHelvetica chimica acta


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