3-Phenyl-5-methyl-2H,5H-furan-2-ones: tuning antifungal activity by varying substituents on the phenyl ring.
A series of racemic 3-phenyl-5-methyl-2H,5H-furan-2-ones related to a natural product, (-)incrustoporine, was synthesized, and their antifungal activity evaluated. The key structural feature, furanone ring, was closed via H2SO4-mediated cyclization of 2-phenylpent-4-enoic acids. The compounds displayed antifungal activity, especially against filamentous fungi. Expressed as the minimum inhibition concentration (MIC) in micromol/L, the activity of the most promising derivative against Absidia corymbifera matched that of ketoconazole (31.25 micromol/L). In terms of microg/mL, the substance was more active (7.6 microg/mL) than this standard antifungal drug (16.6 microg/mL).
Pour
M
M
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic. pour@faf.cuni.cz
Spulák
M
M
Balsánek
V
V
Kunes
J
J
Buchta
V
V
Waisser
K
K
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002722:Chlorobenzenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003500:Cyclization; D015195:Drug Design; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology; D015394:Molecular Structure
C418106:3-(3,4-dichlorophenyl)-5-methyl-2H,5H-furan-2-one; D000935:Antifungal Agents; D002722:Chlorobenzenes; C094022:incrustoporin; D015107:4-Butyrolactone; D007654:Ketoconazole