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Antimicrobial Agents and Chemotherapy, March 2004, p. 873-878, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.873-878.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of 3-(Halogenated Phenyl)-5-Acyloxymethyl- 2,5-Dihydrofuran-2-ones against Common and Emerging Yeasts and Molds

Vladimír Buchta,1* Milan Pour,2 Petra Kubanová,1 Luis Silva,1 Ivan Votruba,3 Marie Voprsálová,4 Radan Schiller,2 Helena Fáková,2 and Marcel Spulák2

Department of Biological and Medical Sciences,1 Department of Inorganic and Organic Chemistry,2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University in Prague, CZ-500 05 Hradec Kralove,4 Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ-16610 Prague 6, Czech Republic3

Received 2 July 2003/ Returned for modification 29 August 2003/ Accepted 10 November 2003

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 <= 2.0 µg/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.

* Corresponding author. Mailing address: Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. Phone: 420 (49) 5067365. Fax: 420 (49) 5518002. E-mail: buchta{at}faf.cuni.cz.

Antimicrobial Agents and Chemotherapy, March 2004, p. 873-878, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.873-878.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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