Bioactive Secondary Metabolites Produced By Two Antarctic Marine-derived Fungi

Due to their unique living environment, antarctic marine-derived microorganisms have been discovered as an important source of bioactive lead compounds which have new structures and unique activities. A study was performed to investigate the bioactive lead compounds derived from Antarctic marine-derived microorganisms by the combination of activity screen and chemistry screen. This thesis describes the study of secondary metabolites produced by two selected Antarctic marine-derived fungi with anti-tumor activities.Fifty-eight fungal strains were isolated from eleven Antarctic marine samples including sponges, seaweeds, seawater, and sea muds which were collected from the Southern Sea. Eight active strains showed cytotoxic activities in brine shrimp lethality assay. Among them, five active strains showed obviously cytotoxic activity in K562 cell-based SRB assay. Two active fungal strains (PRB-2,PR4-1-3), which showed homologue peaks in HPLC fingerprint spectrum and showed anti-tumor activities, were selected for further study of their secondary metabolites.Followed the Large-scale fermentations, the EtOAC extract of the two bioactive fungi were chromatographed by repeated silica gel column, Sephadex LH20, preparative TLC and semi-preparative HPLC, which led to the isolation of fifteen (1-15) and nine compounds (16-24) from the Antarctic marine-derived fungi PRB-2 (Penicillium crustosum) and PR4-1-3 (Penicillin chrysogenum), respectively. Three newγ-butyrolactone derivatives, crustolactones A-C (1-3), were determined based on the physico-chemical properties and spectral data (IR, UV, MS, NMR, etc.). Another 21 known compounds were identified, including five alkaloids (4-7,18), four anthraquinones (8,19-21), six benzol derivatives (9-11,22-24), two secalonic acids diphenyl (16-17) and four other compounds.The new compounds 1-3 were evaluated for their cytotoxic activity, but unfortunately they showed no cytotoxic activity. The antivirus activities of three new compounds 1-3 and two known compounds 16-17 were evaluated by CPE method. Compound 2 and 16 showed weak and moderate antivirus activity, respectively. At the concentration of 50 ug/mL, their inhibition ratio against H1N1 virus equaled to 42.9% and 50%, respectively.Above all, five active Antarctic marine-derived fungi with cytotoxic activities were obtained by combinatorial screening. Twenty four compounds were obtained from two Antarctic marine-derived fungi including three new compounds. The studies provided novel structure types for natural product chemistry. It also proves that the method we used is effective in looking for new bioactive secondary metabolites from Antarctic marine-derived fungi.