3-Phenyl-5-acyloxymethyl-2H,5H-furan-2-ones: Synthesis and biological activity of a novel group of potential antifungal drugs

3-(Substituted phenyl)-5-acyloxymethyl-2H,5H-furan-2-ones related to the na tural product (-)-incrustoporine were synthesized and their in vitro antifu ngal activity evaluated. The compounds with halogen substituents on the phe nyl ring displayed much higher antifungal effect against Aspergillus fumiga tus than selected representatives of azole antifungal drugs. In particular, the activity (1.34,mug/mL) of the most promising derivative, 3-(3,4-dichlo rophenyl)-5-pivaloyloxymethyl-2H,5H-furan-2-one, was comparable to that of amphotericin B (0.5 mug/mL). Preliminary evaluation of the toxicity of the compound was carried out as well. Considering the size and properties of th ese molecules in comparison with those of amphotericin B, further developme nt of this novel group of antifungals may lead to substances with better ph armacological profiles than that of the standard anti-Aspergillus drug.