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dc.contributor.authorJähne, Evelyn A.
dc.contributor.authorEigenmann, Daniela E.
dc.contributor.authorMoradi-Afrapoli, Fahimeh
dc.contributor.authorVerjee, Sheela
dc.contributor.authorButterweck, Veronika
dc.contributor.authorHebeisen, Simon
dc.contributor.authorHettich, Timm
dc.contributor.authorSchlotterbeck, Götz
dc.contributor.authorSmiesko, Martin
dc.contributor.authorHamburger, Matthias
dc.contributor.authorOufir, Mouhssin
dc.date.accessioned2016-10-21T10:35:37Z
dc.date.available2016-10-21T10:35:37Z
dc.date.issued2016
dc.identifier.issn0032-0943
dc.identifier.doi10.1055/s-0042-110323
dc.identifier.urihttp://hdl.handle.net/11654/23406
dc.description.abstractTryptanthrin and (E,​Z)​-​3-​(4-​hydroxy-​3,​5-​dimethoxybenzylidene)​indolinone (indolinone) were recently isolated from Isatis tinctoria as potent anti-​inflammatory and antiallergic alkaloids, and shown to inhibit COX-​2, 5-​LOX catalyzed leukotriene synthesis, and mast cell degranulation at low μM to nM concns. To assess their suitability for oral administration, we screened the compds. in an in vitro intestinal permeability assay using human colonic adenocarcinoma cells. For exact quantification of the compds., validated UPLC-​MS​/MS methods were used. Tryptanthrin displayed high permeability (apparent permeability coeff. > 32.0 × 10-​6 cm​/s) across the cell monolayer. The efflux ratio below 2 (< 1.12) and unchanged apparent permeability coeff. values in the presence of the P-​glycoprotein inhibitor verapamil (50 μM) indicated that tryptanthrin was not involved in P-​glycoprotein interactions. For indolinone, a low recovery was found in the human colon adenocarcinoma cell assay. High-​resoln. mass spectrometry pointed to extensive phase II metab. of indolinone (sulfation and glucuronidation)​. Possible cardiotoxic liability of the compds. was assessed in vitro by measurement of an inhibitory effect on human ether-​a-​go-​go-​related gene tail currents in stably transfected HEK 293 cells using the patch clamp technique. Low human ether-​a-​go-​go-​related gene inhibition was found for tryptanthrin (IC50 > 10 μM) and indolinone (IC50 of 24.96 μM)​. The anal. of compds. using various in silico methods confirmed favorable pharmacokinetic properties, as well as a slight inhibition of the human ether-​a-​go-​go-​related gene potassium channel at micromolar concns.
dc.description.urihttps://www.thieme-connect.de/DOI/DOI?10.1055/s-0042-110323
dc.language.isoen
dc.relation.ispartofPlanta Medica
dc.accessRightsAnonymous
dc.subjectPharmacology
dc.titleCaco-2 Permeability Studies and In Vitro hERG Liability Assessment of Tryptanthrin and Indolinone
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin
dc.volume82
dc.issue13
dc.audienceScience
fhnw.publicationStatePublished
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.InventedHereYes
fhnw.PublishedSwitzerlandNo
fhnw.pagination1192-1201
fhnw.IsStudentsWorkno
fhnw.publicationOnlineJa


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