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Chem Biol Drug Des. 2011 Mar;77(3):212-22. doi: 10.1111/j.1747-0285.2010.01072.x. Epub 2011 Jan 19.

Antifungal activity of xanthones: evaluation of their effect on ergosterol biosynthesis by high-performance liquid chromatography.

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1
Research Center of Medicinal Chemistry - University of Porto (CEQUIMED-UP), R. Aníbal Cunha, 164, 4050-047, Porto, Portugal. epinto@ff.up.pt

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.

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