Secondary Metabolites Of A Jellyfish Nemopilema Nomurai And Associated Fungus Paecilomyces Variotii

Marine organisms are distinguished as a rich source of bioactive natural products with unique structures and various potent pharmacological properties, which has became a mature field. In past decades, study on secondary metabolites from marine microorganism was a rapidly growing field. In this study, I first examined the secondary metabolites of Nemopilema nomurai for subsequent biological evaluation, and then investigated bioactive compounds from the associated fungus Paecilomyces variotii. The planar structures of compounds were established by 1D and 2D NMR and MS analysis. The stereochemistry was defined by CD spectral data, optical rotation, and/or NMR comparison with those of the model compounds. The plausible biosynthetic pathways of the compounds were proposed.Part 1:Secondary metabolites from the jellyfish Nemopilema nomurai.Over the past few years, unusual explosion of population of the giant jellyfish Nemopilema nomurai (Scyphozoa:Rhizostomae) has caused economic and social damages in the waters of China, Korea, and Japan without any definitive reason. Most previous chemical studies on jellyfish focused on their venom. In parallel, several studies have been performed to utilize jellyfish in a productive manner, such as food stuff or agricultural fertilizers. In a bioassay-guided chemical investigation of EtOAc extract of the jellyfish, two new alkoxyglycerols (1 and 2) and a new dicarboxylic acid (8) were isolated, with five known alkoxyglycerols (3-7) and 12 known fatty acids (9-21). Compounds 1 and 2 were evaluated for suppressive effect on the pro-inflammatory mediators (NO, IL-6, and TNF-a) in murine macrophage cells. However, they were found inactive upto the concentration of 100μM. Compound 8 was an unusual dicarboxylic acid with amine group, and was subjected to a cytotoxicity evaluation against a panel of five human solid tumor cell lines (A549, SK-OV-3, SK-MEL-2, XF498, and HCT15) but only marginal cytotoxicity was observed.Part 2:Antibacterial compounds from the fungus Paecilomyces variotii.With the aim of discovering bioactive metabolites from jellyfish-derived microorganisms, I initiated chemical investigation of a fungus derived from the giant jellyfish Nemopilema nomurai. In the bioactivity-guided chemical study of the fungus Paecilomyces variotii, four new polyketides (22-25) and five known compounds (26-30) were isolated from the EtOAc extract. Compound 25 was first isolated from natural source. Compounds 22-24 were evaluated for their inhibitory activity against pathogenic bacteria including methicillin-resistant Staphylococcus aureus 3089 (MRSA) and multidrug-resistant (MDR) Vibrio parahaemolyticus 7001 to exhibit the MIC values in the range of 5-40μg/mL. Compound 26 was isolated from a natural source for the first time and was evaluated for antibacterial activity against human and marine pathogens, including MDR (multi-drug-resistant) strains. Compound 26 exhibited mild antibacterial activity against Escherichia coli DC 2, Streptococcus iniae, and methicillin-resistant Staphylococcus aureus 3089 (MRSA). Viriditoxin (28) showed significant antibacterial activity against several marine and human pathogens including MDR strains. Significant potencies against resistant pathogens such as MDR Enterococcus faecium, MDR Enterococcus faecalis, and MRSA were highly interesting. Viriditoxin also showed notable antibacterial activity against the fish pathogen Streptococcus iniae. Its potency was over 100-fold higher than oxytetracycline which is employed as a general antibiotic for aquaculture.