Study On Secondary Metabolites From Two Marine-derived Fungi Westerdykella Dispersa And Phomopsis Lithocarpus And Their Biological Activities

Marine-derived microorganisms survive in the extreme environment of high salt,high pressure,under cold and hypoxia and form peculiar metabolic pathways,which results in a variety of pharmacological natural products.To data,some active compounds obtained from marine microorganisms have been applied to clinical therapy.As an important part of marine microorganisms,marine-derived fungi are regarded as a significant source for the discovery of pharmaceutical lead compounds,presumably attributable to their structurally unique and biologically active secondary metabolites.In order to search for highly bioactive secondary metabolites,a comprehensive investigation on two marine fungal strains?Westerdykella dispersa FS350 and Phomopsis lithocarpus FS580?was carried out.Most of isolates were screened on their cytotoxic,antioxidant,anti-microbial and?-glucosidase enzyme inhibitory activities.28 compounds were isolated from the fermentation extracts of two marine-derived fungal strains?Westerdykella dispersa FS350 and Phomopsis lithocarpus FS580?using various chromatographic methods including silica gel column chromatography,RP-18 chromatography,Sephadex-LH20 column chromatography and HPLC.The relative and absolute configuration of these compounds were elucidated by means of extensive analysis of spectroscopic techniques such as ESI-MS,HR-ESI-MS,¹H-NMR,¹³C-NMR,1H-1H COSY,HSQC,HMBC,NOESY and X-ray diffraction.Among 28 secondary metabolites,there are ten new compounds including a new skeleton?Figure 1?.All of the isolates were tested for their cytototxic activities against HepG-2 MCF-7,SF-268,NCI-H460 cell lines,and the active compounds were further measured for their IC₅₀0 values.The anti-microbial activities of 20 compounds were evaluated against Staphylococcus aureus,Escherichia coli,Bacillus subtilis,Alternaria alternata,Cylindrocladium sp.,Curvularia lunata and Colletotrichum gloeosporioides by filter paper diffusion method,and some compounds were also tested for their antioxidant and anti-?-glucosidase activities.The results indicated that compounds 11,12,13,25,26,27 and 28 exhibited moderate cytotoxicity against SF-268,MCF-7 and HepG-2 cell lines.Compound 11 showed cytotoxic activity against three tested tumor cell lines with IC₅₀ values of23.1,19.2,27.2?M,respectively;compound 12 displayed cytotoxicity against three tumor cell lines with IC₅₀ values of 24.6,23.7,27.4?M,respectively;compound 13 exhibited cytotoxic effect against three tumor cell lines with IC₅₀ values of 24.5,23.2,25.0?M,respectively.Compounds 27 and 28 displayed moderate cytotoxic activity against the three tested tumor cell lines with IC₅₀ values of 21.6,17.0,19.5?M and18.4,18.5,19.0?M,respectively,while 25 and 26 showed inhibitory effect with the IC₅₀ values ranging from 33.0 to 52.2?M.Eight compounds?1-8?showed weak antioxidant activity.Compounds 9-28exhibited no significant anti-microbial activity and compounds 25-28displayed no?-glucosidase inhibitory effect.In conclusion,8 known compounds?1-8?were isolated and identified from Westerdykella dispersa FS350,and 20 compounds?9-28?were obtained from Phomopsis lithocarpus FS508,including 10 new compounds and a new skeleton.Among them,the absolute configurations of 4 compounds were confirmed by single-crystal X-ray diffraction analysis and 7 compounds showed moderate cytotoxic activity.This study provides a scientific theoretical basis for the development and use of marine fungi.