| Abstract
| - Coruscanone A, a plant-derived cyclopentenedione derivative, showed potent in vitro antifungal activityagainst Candida albicans and Cryptococcus neoformans comparable to amphotericin B and fluconazole. Aseries of analogues have been synthesized by modification of the cyclopentenedione ring, the enolic methoxyfunctionality, and the side chain styryl moiety of this natural product lead. A structurally close1,4-benzoquinone analogue was also prepared. All the compounds were examined for their in vitro activityagainst major opportunistic fungal pathogens including C. albicans, C. neoformans, and Aspergillus fumigatusand fluconazole-resistant C. albicans strains, with several analogues demonstrating potent antifungal activity.Structure−activity relationship studies indicate that the 2-methoxymethylenecyclopent-4-ene-1,3-dionestructural moiety is the pharmacophore responsible for the antifungal activity of this class of compoundswhile the side chain styryl-like moiety plays an important complementary role, presumably contributing totarget binding.
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