Planta Med 2014; 80 - LP1
DOI: 10.1055/s-0034-1395072

HCV NS3/4A protease inhibitory alternariol derivatives from Alternaria alternata, an endophytic fungus residing in red sea soft coral

U Hawas 1, LA El-Kassem 2, W Ahmed 3
  • 1Marine Chemistry Department, Faculty of Marine Sciences, King Abdulaziz University, P. O. Box 80207, Jeddah 21589, Kingdom of Saudi Arabia
  • 2Department of Pharmacognosy, National Research Centre, Dokki, Cairo, Egypt
  • 3Chemistry of Natural and Microbial Products Department, National Research Centre, Dokki-12311, Cairo, Egypt

Marine endophytic fungi are being considered as a big but nearly untapped microbial reservoir that can be expected to provide a wide variety of structurally unique and biologically potent natural products [1,2]. 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 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 good inhibition of HCV protease (IC50 14.0 µg/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 its culture broth afforded alternariol-9-methylether-3-O-sulphate (1) alternariol-9-methylether (2), alternariol (3), maculosin (4), and maculosin-5 (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 protease as well as anti-cancer and antimicrobial activities.

Keywords: Alternaria alternata, alternariol sulphate, HCV protease

References:

[1] Strobel, G. et al. (2004)J Nat Prod 67: 257 – 268.

[2] Zhang, H. W. et al. (2006) Nat Prod Rep 23: 753 – 771.