The Antitumor Constituents Of Secondary Metabolites Produced By Two Deep-sea-sediment Derived Fungi

Deep-sea derived microorganisms have been considered as an important source of bioactive leading compounds, due to their unique living environment. A study was carried out to investigate the bioactive lead compounds derived from deep-sea derived microorganisms. This thesis describes the studies of secondary metabolites produced by two selected deep-sea derived fungi with anti-tumor activities.One hundred and eight microorganism strains were isolated from twenty deep-sea sediments samples which were collected from the deep Pacific. Twenty-two active strains (ten actinomycetes and twelve fungi) showed cytotoxic activities on P388 cell line by the SRB method, with nice HPLC and TLC finger-print spectrums. After optimized the fermentation conditions, two fungi (ZLN-57,ZLN-60) were selected for further study for the rich secondary metabolites, which had the HPLC fingerprint spectrum with same homologue peaks and showed anti-tumor activities. Meanwhile, we also investigated another two deep-sea derived fungi, with small-scale fermentation preliminary.Followed the Large-scale fermentations, the EtOAC extract of the two bioactive strains were chromatographed by repeated silica gel column, Sephadex LH20, preparative TLC and semi-preparative HPLC, which lead to the isolation of twenty (1-17,29-31) and twelve compounds (18-25,32-35) from the deep-sea derived fungi ZLN-57(Penicillium griseofulvum) and ZLN-60, respectively. In addition, one (26) and six (27-28,36-39) compounds were also isolated from the Deep-sea derived fungi strains ZLN-30 and ZLN-29, respectively.Eight new compounds, including indole diketopiperazine alkaloids (1-3), diphenyl ethers (19-22), and cyclopeptides (23) were determined based on the physico-chemical properties and spectral data (IR, UV, MS, NMR, etc.), togethe with 20 known compounds, identified as nine indole diketopiperazine alkaloids (4-12), one indole aldehyde derivative (13), five benzol derivatives (14-16,24,28), one diphenyl ethers (18), one cerebroside (25) and three polyketones (17,26,27).The new compounds 1-3 were evaluated for their radical scavenging activities against DPPH. Compounds 1-3 showed weak activities with IC5o values of 135,120 and 91μM, respectively (ascorbic acid as positive control, IC50 26μM). The evaluations of anti-tumor activities of the rest new compounds are still keep going.Summararily, Twenty-two active deep-sea derived strains with cytotoxic activities were obtained by combinatorial screening. Twenty eight compounds were obtained from the deep-sea derived fungi with eight 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 deep-sea derived fungi.