Synergistic Anti- Activity of Bengazole A in the Presence of Bengamide A †.

Bengazoles A⁻G from the marine sponge sp. exhibit potent in vitro antifungal activity against spp. and other pathogenic fungi. The mechanism of action (MOA) of bengazole A was explored in under both liquid culture and surface culture on Mueller-Hinton agar. Pronounced dose-dependent synergistic antifungal activity was observed with bengazole A in the presence of bengamide A, which is also a natural product from sp. The MOA of bengazole A was further explored by monitoring the sterol composition of in the presence of sub-lethal concentrations of bengazole A. The GCMS of solvent extracts prepared from liquid cultures of in the presence of clotrimazole-a clinically approved azole antifungal drug that suppresses ergosterol biosynthesis by the inhibition of 14α-demethylase-showed reduced cellular ergosterol content and increased concentrations of lanosterol and 24-methylenedihydrolanosterol (a shunt metabolite of ergosterol biosynthesis). No change in relative sterol composition was observed when was cultured with bengazole A. These results eliminate an azole-like MOA for the bengazoles, and suggest that another as-yet unidentified mechanism is operative.