title: 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.
abstract: 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.
authors.affiliation: 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
authors.forename: Milan
authors.initials: M
authors.lastname: Pour
authors.forename: Marcel
authors.initials: M
authors.lastname: Spulák
authors.forename: Vojtech
authors.initials: V
authors.lastname: Balsánek
authors.forename: Jirí
authors.initials: J
authors.lastname: Kunes
authors.forename: Petra
authors.initials: P
authors.lastname: Kubanová
authors.forename: Vladimír
authors.initials: V
authors.lastname: Buchta
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D005663:Furans; C094022:incrustoporin; D015107:4-Butyrolactone