Alternariol Derivatives from Alternaria alternata, an Endophytic Fungus Residing in Red Sea Soft Coral, Inhibit HCV NS3/4A Protease

Three fungal strains, Alternaria alternata, Eurotium chevalieri and Penicillium crustosum were isolated from the normal tissues of the soft coral Litophyton arboreum, collected from the Egyptian Red Sea coast. The ethyl acetate (EtOAc) extracts of their liquid cultures were subjected to primary screening of anticancer and inhibition of hepatitis C virus (HCV) NS3-NS4A protease. As a result, A. alternata showing a high-level inhibition of HCV protease (IC50 14.0 mu g/mL) was selected for further investigation on its secondary metabolites. The fungus was identified by its morphology and 18S rDNA. Bioassay-guided fractionation of the EtOAc extract of A. alternata culture broth revealed 5 metabolites: alternariol-9-methyl ether-3-O-sulphate, alternariol-9-methyl ether, alternariol, maculosin and maculosin-5. The structures of these metabolites were assigned on the basis of detailed spectroscopic analysis. The biological properties of the isolated compounds were explored for inhibition of HCV NS3-NS4A protease as well as anticancer and antimicrobial activities.