Antifungal compounds from four marine sponges

Abstract

Screening a large number of organic extracts of marine sponges from the National Cancer Institute Open Repository for antifungal drug discovery produced potent hits for bioassay-guided fractionation. We have shown that the phloeodictines from the marine sponge Pellina eusiphonia and the microsclerodermins from Microscleroderma herdmani exhibited broad spectrum antifungal activities against fungal pathogens including drug-resistant strains. Our continued efforts in this regard have led to the identification of the cyclic peptide aciculitin B from Aciculites ciliate that showed remarkable in vitro antifungal activity against the clinically important fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. Its potency against C. neoformans is 60-fold stronger than the antifungal drug amphotericin B. We have also isolated the antifungal compounds including the tetramic acid glycoside aurantoside E from Plakinolopha mirabilis, 4α-isocyanogorgon-11-ene from Axinyssa terpinis, and the biphenyl ether 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol from an unidentified sponge. These compounds may be used as molecular probes to uncover novel antifungal drug targets or as leads for preparation of new compounds with improved antifungal properties.