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 natural product (-)incrustoporine were synthesized and their in vitro antifungal activity evaluated. The compounds with halogen substituents on the phenyl ring displayed much higher antifungal effect against Aspergillus fumigatus than selected representatives of azole antifungal drugs. In particular, the activity (1.34 microg/mL) of the most promising derivative, 3-(3,4-dichlorophenyl)-5-pivaloyloxymethyl-2H,5H-furan-2-one, was comparable to that of amphotericin B (0.5 microg/mL). Preliminary evaluation of the toxicity of the compound was carried out as well. Considering the size and properties of these molecules in comparison with those of amphotericin B, further development of this novel group of antifungals may lead to substances with better pharmacological profiles than that of the standard anti-Aspergillus drug.
Pour
M
M
Laboratory of Structure and Interactions of Biologically Active Molecules, Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, Czech Republic. pour@faf.cuni.cz
Spulák
M
M
Buchta
V
V
Kubanová
P
P
Voprsalová
M
M
Wsól
V
V
Fáková
H
H
Koudelka
P
P
Pourová
H
H
Schiller
R
R
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C433817:3-(3,4-dichlorophenyl)-5-pivaloylmethyl-2H,5H-furan-2-one; D000935:Antifungal Agents; D005663:Furans; D000666:Amphotericin B; D015107:4-Butyrolactone