Antifungal effect and possible mode of activity of a compound from the marine sponge Dysidea herbacea

Objectives. Assessment of antifungal activity of a compound isolated from the marine sponge Dysidea herbacea against the fungal pathogens Candida (primarily C. albicans) and Aspergillus (primarily A. fumigatus) species, and investigations of the possible mode of activity of the compound. Methods. Freeze dried sponges were extracted with EtOAc-MeOH. Bioassay guided separation was used to identify the active compound. Antifungal activity was assessed in vitro by a modified NCCLS technique. For determination of the possible mode of activity of the compound we tested the effect on fungal cellular morphology (tight, scanning and transmission electron microscopy) and possible site of activity in the fungal cells, such as cell membrane (ion leakage kinetics) as well as toxicity (cytotoxicity tests). Results and conclusions. The active compound was determined to be 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy) phenol. This compound exhibited in vitro activity against the tested fungal pathogens. The experiments on the mode of activity revealed that there are significant changes in fungal cell morphology, as demonstrated by scanning and transmission electron microscopy. The compound, apparently, affects the fungal cell membrane, expressed primarily in Leakage of potassium ions from the fungal cells. Two other bromo diphenyl ethers were also found to be active. Further experiments in in vivo models are planned. (c) 2004 The British Infection Society. Published by Elsevier Ltd. All rights reserved.