Chiral derivatives of Butenafine and Terbinafine: synthesis and antifungal activity |
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Authors: | Erik Fuglseth,Hanne Hø gmoen,Eirik Sundby,Bå rd Helge Hoff |
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Affiliation: | a Department of Chemistry, Norwegian University of Science and Technology, Høgskoleringen 5, NO-7491 Trondheim, Norway b Oslo University College, PO Box 4, St. Olavs Plass, 0130 Oslo, Norway c Sør-Trøndelag University College, E.C. Dahls Gate 2, 7004 Trondheim, Norway |
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Abstract: | Two series of allylamines/benzylamines have been synthesised and evaluated for their antifungal activity towards Cryptococcus neoformans. All compounds are chiral derivatives of Butenafine and Terbinafine, having additional substituents at the carbon connected to the central nitrogen atom. In both series, the antifungal activity was strongly dependent on both the steric bulk and the electronic nature of the substituents. Compared to the parent compounds (Butenafine and Terbinafine), the activity was maintained when the hydrogen was replaced with a methyl group. Lower activity was observed for ethyl, whereas introduction of -CH2F, -CHF2, -CF3 or -CN substituents removed all antifungal activity. Testing of (R)- and (S)-N-(4-tert-butylbenzyl)-N-methyl-1-(naphthalen-1-yl)ethanamine against C. neoformans, Cryptococcus diffluens and Trichosporon cutaneum revealed that most of the activity resides in the (R)-enantiomer. The (R)-enantiomer performed as well as, or better (lower MIC values) than Butenafine against each test strain, suggesting that antimycotics based on this compound might be an improvement of existing Butenafine-based formulations. |
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Keywords: | Antifungal agents Amines Substituent effects Chiral Butenafine |
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