[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.
Chemical Biology & Drug Design 03/2011; 77(3):212-22. · 2.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: The enzyme steroid sulfatase (STS) activity is high in breast tumors and elevated levels of STS mRNA expression have been
associated with a poor prognosis. Potent STS irreversible inhibitors have been developed, paving the way to use this new type
of therapy for breast cancer. Synthetic small molecules belonging to a focused library of inhibitors of tumor cell growth
already obtained and new molecules planned to be reversible inhibitors of STS were docked into STS using the program AutoDock
4. To guide the docking process of the select ligands through the lattice volume that divides the receptor’s area of interest,
a full set of grid maps was built using the program AutoGrid. Some of the new designed small molecules showed calculated binding
affinity for STS presenting ΔG values in a range of -11.15 to -13.07 kcal.mol− 1. The synthesis of the most promising STS inhibitors, based on these results, is in progress.
Advances in Bioinformatics - 4th International Workshop on Practical Applications of Computational Biology and Bioinformatics 2010 (IWPACBB 2010), Guimarães, Portugal, 16-18 June 2010; 01/2010
[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.
Letters in Drug Design & Discovery 01/2010; · 0.85 Impact Factor