Synthesis and structure-antifungal activity relationships of 3-aryl-5-alkyl-2,5-dihydrofuran-2-ones and their carbanalogues: further refinement of tentative pharmacophore group.
Two series of 3-(substituted phenyl)-5-alkyl-2,5-dihydrofuran-2-ones related to a natural product, (-)incrustoporine, were synthesized and their in vitro antifungal activity evaluated. The compounds with halogen substituents on the phenyl ring exhibited selective antifungal activity against the filamentous strains of Absidia corymbifera and Aspergillus fumigatus. On the other hand, the influence of the length of the alkyl chain at C(5) was marginal. The antifungal effect of the most active compound against the above strains was higher than that of ketoconazole, and close to that of amphotericin B. In order to verify the hypothesis about a possible relationship between the Michael-accepting ability of the compounds and their antifungal activity, a series of simple carbanalogues, 2-(substituted phenyl)cyclopent-2-enones, was prepared and subjected to antifungal activity assay as well.
Pour
Milan
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
Marcel
M
Balsánek
Vojtech
V
Kunes
Jirí
J
Kubanová
Petra
P
Buchta
Vladimír
V
D015107:4-Butyrolactone / Q000031:analogs & derivatives*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D015003:Yeasts / Q000187:drug effects
D000935:Antifungal Agents; D005663:Furans; C094022:incrustoporin; D015107:4-Butyrolactone