The Secondary Metabolites And Their Bioactivities Of Zoanthid Palythoa Haddoni-Derived Fungus Cochliobolus Hawaiiensis

Marine-derived microorganisms have become the most important bioresources for screening and discovery of marine natural products and marine drugs. Investigation on marine-derived fungi mainly focused on sponges and ascidians. In recent years the study on coral-derived fungi has aroused great concern, and mainly for Octocorallia (such as soft corals, gorgonian, etc.). yet that for the Hexacorallia still limited.In our former study, systematic research on the phylogenetic diversity and antibacterial activity of fungi derived from zoanthids in the South China Sea has been done. And a series of antifouling and fungicidal 14-membered resorcylic acid lactones were obtained from the zoanthid Palythoa haddoni-derived fungus Cochliobolus lunatus (TA26-46).In this study, screening of antifungal activities of the extracts of 10 zoanthid Palythoa haddoni-derived fungi which have close phylogenetic relationship with Cochliobolus lunatus (TA26-46) leads to the finding of Cochliobolus hawaiiensis (TA26-15). Its extract exihibits potent antifungal activity. In this paper, the bioactive secondary metabolites from Cochliobolus hawaiiensis (TA26-15) were investigated according to the modern technology of marine natural products. And 17 compouds were separated from it, including 9 sordarin diterpene glycoside derivatives 1-9,3 coumarins 10-12,5 ergot steroids 13-17, among which 2-7,9 are new compounds. New compouds are varied in aldehyde group in diterpenoid skeleton and carboxyl group in 2-hydroxysebacic acid with different length. For new compounds, the plane structures were determined by 1D/2D NMR combined with MS data, and the relative configurations by NOESY, NOE and the coupling constants.The bioactive compounds from Cochliobolus hawaiiensis (TA26-15) were evaluated by the following models:antifungal, antibacterial, lethal activity to brine shrimp (Artimia salina), cytotoxic activity and antiviral models. The sordarin diterpene glycoside derivatives showed selective antifungal activity against C. albicans ATCC10231. Compounds 1 and 2 exhibited potent antifungal activity against C. albicans ATCC 10231 with the MIC values of 3.68μM and 2.86μM. The antifungal activity against C. albicans ATCC 10231 of 3-9 reduced with the MIC values of 14.87 μM,12.69 μM,11.94μM,9.76μM,8.67μM,18.29μM and 23.78 μM compraring with that of 1 and 2. The lower activity of compounds 8 and 9 indicated that the sugar substrate play the important role in antifungal activity. The sordarin diterpene glycoside derivatives showed non lethal activity to brine shrimp (Artimia salina) nor cytotoxicity.In summary,17 compounds were obtained from the secondary metabolites from Zoanthid p. haddoni-derived Cochliobolus hawaiiensis (TA26-15), mainly including terpenes, coumarins and ergot steroids, and there were 7 new compounds among them. The sordarin diterpene derivatives showed selective antifungal activity against C. albicans ATCC 10231.