Studies On The Secondary Metabolites Of Two Marine-Derived Fungi

Marine-derived halotolerant fungi are a rich source of secondary metaboliteswith diverse structures and biological activities. The Yellow River Delta is a typicalcoastal wetland, which possesses a complex ecosystem and rich biodiversity due tothe interaction of land and sea. Although the microorganisms in this specialenvironment might be an important source for structurally new and bioactivecompounds, little research on secondary metabolites from these microbes has beenundertaken. South China Sea has been a hot area of the natural products research.While sponge as an important source of marine natural products have been attractingwide spread attention. To search for structurally novel and biologically activecompounds from the secondary metabolites of halotolerant fungal strains, a study iscarried out to investigate the compounds derived from the crude extracts of the strainsisolated from the two districts. Studies include isolation of fungal strains fromsamples and activity screening, selecting strains and optimization of fermentationconditions, fractionation of the pure compounds, structural elucidation and biologicalactivities evaluation of pure compounds.67fungal strains were isolated from three deep soil samples and three spongesamples, which were collected from the subway exploration phreatic in Qingdao andXisha Islands in the South China Sea, respectively. Besides, three halotolerant fungalstrains isolated from the Yellow River Delta were also investigated. Two strains werepicked out based on the cytotoxic assay using the P388cell line by the SRB methodand on the HPLC and TLC chemical screening. The stain HK14-01was identified asPenicillium chrysogenum while1051#was identified as Aspergillus candidus.After optimization of fermentation conditions, the two strains were fermented inlarge-scale, respectively. By means of chromatography over silica gel column,Sephadex LH20, preparative TLC and semi-preparative HPLC,23compounds (1-23)were isolated from the whole crude extracts. By means of physic-chemical properties and spectral analysis (IR, UV, MS,NMR, X-ray, CD), structures of23pure compounds were respectively determined.Among them, there were ten polyhydroxy-p-terphenyls compounds, one of them wasa new compounds. We defined the absolute configuration of structure unique activecompound oxaline for the first time by the X-ray single crystal diffraction and CDcurve. The absolute configuration of compound2was determined for the first time inour work.The antibacterial activity of these compounds was evaluated by paper diskmethod. The cytotoxicity of these compounds against several cancer cell lines wasevaluated by SRB and MTT method. The anti-inflammatory activities of thep-terphenyls compounds were also tested.Summarily, this work obtained two halotolerant fungal strains by integratedscreening, and23compounds were obtained from cultures of them, including one newcompound. This study provides novel structure types for natural product chemistryand bioactive template compounds for exploring new drugs. It also proves thatmarine-derived halotolerant fungi are an affluent resource for searching for newbioactive secondary metabolites.