[Show abstract][Hide abstract] ABSTRACT: The increasing resistance of pathogenic fungi to antifungal compounds and the reduced number of available drugs led to the search for therapeutic alternatives among natural products, including xanthones. The antifungal activity of 27 simple oxygenated xanthones was evaluated by determination of their minimal inhibitory concentration on clinical and type strains of Candida, Cryptococcus, Aspergillus and dermatophytes, and their preponderance on the dermatophytic filamentous fungi was observed. Furthermore, a simple and efficient HPLC method with UV detection to study the effect of the active xanthones on the biosynthesis of ergosterol was developed and validated. Using this methodology, the identification and quantification of fungal sterols in whole cells of Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and Trichophyton mentagrophytes were accomplished. In summary, 1,2-dihydroxyxanthone was found to be the most active compound against all strains tested, showing its effect on sterol biosynthesis by reducing the amount of ergosterol detected.
Full-text · Article · Mar 2011 · Chemical Biology & Drug Design
[Show abstract][Hide abstract] ABSTRACT: The synthesis of two new sulfated xanthones and two O-substituted benzophenones was carried out to evaluate for their inhibitory effect on growth of human tumor cell lines. The sulfation of 3,6-(2) and 3,4-dihydroxyxanthone (3) was accomplished using sulfur trioxide-pyridine to give, respectively, xanthone-3,6-O,O-bis(sulfate) (4) and xanthone-3,4-O,O-bis(sulfate) (5). Treatment of 2,2',4,4'-tetrahydroxybenzophenone (6) with acetic acid and prenyl bromide fur-nished 2,2',4,4'-tetraacetoxybenzophenone (7) and (5-hydroxy-2,2-dimethylchroman-6-yl)(2'-hydroxy-4'-(tert-pentyloxy)phenyl)methanone (8), respectively. Compounds 2-8 were tested for their effect on the in vitro growth of four representative human tumor cell lines: MCF-7 ER(+) (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), SF-268 (glioma), and A375-C5 (melanoma). Compounds 2 and 7-8 showed an inhibitory activity in the M range.
Full-text · Article · Aug 2010 · Letters in Drug Design & Discovery