Secondary Metabolites Of Five Marine-derived Fungi And Their Bioactivities

In this dissertation, five fungal strains including Chaetomium globosum EN-14 (derived from the marine green alga Ulva pertusa), Aspergillus ochraceus EN-31 (derived from the marine brown alga Sargassum kjellmanianum), Aspergillus sydowii EN-50 (isolated from a tropical marine brown algal of the genus Sargassum), Aspergillus versicolor EN-150 (isolated from the brown algae Scytosiphon lomentarius), and Aspergillus sp. SD-43 (isolated from the sediment collected at E704 of southern China sea, 20°14.538′N, 114°44.683′E) were selected as aimed strains to be fermented for further investigation of chemical constituents. Most of the isolated compounds were preliminary screened on their bioactivities.The compounds were isolated from the fermentation extracts by repeated column chromatography (CC) on silica gel, RP-18, and Sephadex LH-20, as well as by preparative thin layer chromatography (PTLC), semi-preparative HPLC and recrystallization. The structures of these compounds were elucidated by means of spectroscopic methods including IR, UV, EI-MS, FAB-MS, HR-ESI-MS, 1D-NMR (1H-NMR, 13C-NMR, DEPT) and 2D-NMR (1H-1H COSY, HMBC, HMQC) as well as by chemical method. Totally, 93 compounds were isolated and structurally elucidated. From the extracts of C. globosum EN-14, 16 compounds were isolated and structurally elucidated. Among them, seven cytochalasan alkaloids were found to be new compounds (CG1~CG7). From the extracts of A. ochraceus EN-31, 23 compounds were isolated and structurally elucidated. Among them, one benzodiazepine analogue AO1, and three steroids (including a novel steroid with an unprecedented B-nor / B-δ-lactone system) were found to be new compounds (AO11~AO13). And one new naturally occurring product AO7 was also isolated. From the extracts of A. sydowii EN-50, 20 compounds were isolated and structurally elucidated. Among them, three polyketides (AS1, AS2, AS6), and one ceramide derivative (AS7) were found to be new compounds. From the extracts of A. versicolor EN-150, 11 compounds were isolated and structurally elucidated. From the extracts of Aspergillus sp. SD-43, 23 compounds were isolated and structurally elucidated.Some of the pure compounds were screened for their antimicrobial, DPPH scavenging and cytotoxic activities. In the in vitro cytotoxic assay, the new compounds CG3 and CG4 exhibited moderate cytotoxic activities against human lung cancer cell line A-549 (IC50 1.2, 1.3μg/mL, respectively). The novel compounds AO11 showed cytotoxic activities against tumor cell lines sw1990 (human bile duct carcinoma cell line), NCI-H460 (human non-small cell lung cancer cell line), and SMMC-7721 (human hepatoma cell line) (IC50 28.0, 5.0, 7.0μg/mL, respectively). The new compounds AO1 and AO12 showed cytotoxic activities against tumor cell line SMMC-7721 (IC50 10.0, 28.0μg/mL, respectively).The new compound AS7 showed weak lethal activity against brine shrimp larvae with corrected mortality of 61.5% at the concentration 50μg/mL. In the antimicrobial assays, compounds AS8, AV3, AV6, AV9, and AV10 exhibited weak activities against Aspergillus niger at the concentration of 100μg/disk, with inhibition zone ofφ= 8.0, 7.0, 8.0, 8.0, and 9.0 mm, respectively. Compounds AP5, AP7, and AP8 showed weak activities against Alternaria brassicae (berk.) Sace at the concentration of 100μg/disk, with inhibition zone ofφ= 8.0, 8.0, and 7.0 mm, respectively. Compounds AP2, AP3, and AP9 exhibited weak activities against Staphylococcus aureus at the concentration of 100μg/disk, with inhibition zone ofφ= 6.0, 7.0, and 6.0 mm, respectively. Compounds AV7 and AP9 showed weak activities against Escherichia coli at the concentration of 100μg/disk, with inhibition zone ofφ= 6.0 and 7.0 mm, respectively. In the DPPH scavenging assay, compound AO1 exhibited strong free radical scavenging activities with an EC50 of 9.9μM, compared with EC50 of 88.2μM for positive control BHT.In this dissertation, secondary metabolites of five strains of marine fungi were thoroughly studied. It enriched the chemical structures of marine natural products. Though bioassay, 19 compounds were found to be active. It may be helpful to exploration of marine microorganisms.