In vitro activities of 3-(halogenated phenyl)-5-acyloxymethyl- 2,5-dihydrofuran-2-ones against common and emerging yeasts and molds.
Three 3-(halogenated phenyl)-5-acyloxymethyl-2,5-dihydrofuran-2-ones were evaluated for activity against 191 strains of common and emerging yeasts and Aspergillus species by the broth microdilution test performed according to NCCLS guidelines. The furanone derivatives displayed broad-spectrum in vitro activity against potentially pathogenic yeasts and molds, especially Aspergillus spp. (MIC <or= 2.0 microg/ml) and fluconazole-resistant yeast isolates, including Candida glabrata and Saccharomyces cerevisiae. The 4-bromophenyl derivative was the most effective derivative against the majority of species tested, except for the Candida tropicalis and C. glabrata strains, which were more susceptible to the 3-chlorophenyl derivative. The 3,4-dichlorophenyl derivative possessed a lesser in vitro antifungal effect. The potential of further experiments on animal infection and clinical studies is supported by the relatively low cytotoxicity and acute toxicity of the 4-bromophenyl compound. Thus, the halogenated 3-phenyl-5-acyloxymethyl derivatives of 2,5-dihydrofuran-2-one represent a novel, promising group of compounds with significant activity against relevant opportunistic fungi that are pathogenic to humans.
Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University in Prague, CZ-500 05 Hradec Kralove, Czech Republic. buchta@faf.cuni.cz
Vladimír
V
Buchta
Milan
M
Pour
Petra
P
Kubanová
Luis
L
Silva
Ivan
I
Votruba
Marie
M
Voprsálová
Radan
R
Schiller
Helena
H
Fáková
Marcel
M
Spulák
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000494:pharmacology; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects* / Q000648:ultrastructure; D005663:Furans / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D007928:Lethal Dose 50; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000382:microbiology; D015003:Yeasts / Q000187:drug effects* / Q000648:ultrastructure
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D005663:Furans; D015725:Fluconazole