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dc.contributor.authorTvedt, Thor Håkon Kraneen_US
dc.contributor.authorKaasa, Kristinen_US
dc.contributor.authorSundby, Eriken_US
dc.contributor.authorCharnock, Colinen_US
dc.contributor.authorHoff, Bård Helgeen_US
dc.date.accessioned2014-03-19T09:36:43Z
dc.date.available2014-03-19T09:36:43Z
dc.date.issued2013-10en_US
dc.identifier.citationT.H. Krane Thvedt, K. Kaasa, E. Sundby, C. Charnock, B.H. Hoff, Chiral N -benzyl- N -methyl-1-(naphthalen-1-yl)ethanamines and their in vitro antifungal activity against C. neoformans, T.mentagrophytes and T. rubrum , European Journal of Medicinal Chemistry (2013), doi: 10.1016/j.ejmech.2013.07.043en_US
dc.identifier.issn0223-5234en_US
dc.identifier.otherFRIDAID 1061510en_US
dc.identifier.urihttps://hdl.handle.net/10642/1899
dc.description.abstractIn the search for new antifungal compounds and to explore structure activity relationships, a series of 24 chiral benzyl amine type antifungals was synthesised and characterised. In vitro testing against the human pathogen Cryptococcus neoformans revealed that several derivatives had MIC50 values similar to that of the commercial drug Butenafine. All of these contained a bulky group in the para position of the benzyl fragment. Eighteen compounds were also tested for activity against the dermatophytes Trichophyton mentagrophytes and Trichophyton rubrum. Of these (R)-N-(4-tert-butylbenzyl)-N-methyl-1-(naphthalen-1-yl)ethanamine (MIC50: 0.06 μg/mL) and a para-benzyloxy substituted derivative (MIC50: 0.125 μg/mL) possessed high activity. Testing of derivatives with a stereocentre at the benzylic carbon, revealed that (S)-stereochemistry was required for potency: a MIC50 value of 1 μg/mL was obtained for (S)-1-(4-tert-butylphenyl)-N-methyl-N-(naphthalen-1-ylmethyl)ethanamine. Preparation of the corresponding fluoromethyl compound was achieved employing lipase B from Candida antarctica as catalyst in the key step. A low antifungal activity was observed for the fluorinated derivative indicating the importance of the amine basicity for the antifungal potency of these compounds.en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.ispartofseriesEuropean Journal of Medicinal Chemistry;68en_US
dc.subjectAntifungal agentsen_US
dc.subjectSqualene epoxidaseen_US
dc.subjectCryptococcus neoformansen_US
dc.subjectTrichophyton mentagrophytesen_US
dc.subjectTrichophyton rubrumen_US
dc.subjectLipase B from Candida antarcticaen_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk biokjemi: 726en_US
dc.titleChiral N-benzyl-N-methyl-1-(naphthalen-1-yl)ethanamines and their in vitro antifungal activity against Cryptococcus neoformans, Trichophyton mentagrophytes and Trichophyton rubrumen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.version“NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Medicinal Chemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in: T.H. Krane Thvedt, K. Kaasa, E. Sundby, C. Charnock, B.H. Hoff, Chiral N -benzyl- N -methyl-1-(naphthalen-1-yl)ethanamines and their in vitro antifungal activity against C. neoformans, T.mentagrophytes and T. rubrum, European Journal of Medicinal Chemistry (2013), doi: 10.1016/j.ejmech.2013.07.043"en_US
dc.identifier.doihttp://dx.doi.org/10.1016/j.ejmech.2013.07.043


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