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Because of the special living environment, marine-derived microorganisms possess distinct and complex metabolic capabilities, resulting in wide diversity of their secondary metabolites in chemical structure and biological activity. Thus, marine-derived microorganism becomes one of the important resources of active lead compounds. This thesis describes the screening of cytotoxic marine-derived microorganism and the secondary metabolites produced by two selected deep sea sediment-derived fungi. Studies include isolation of actinomyces and fungi from marine water and sediments samples, screening of cytotoxic strains, selecting aimed strains, fermentation studies, bioassay-guided fractionation, structural elucidation and preliminary evaluation in vitro for anti-tumor activities of pure compounds.Using MTT or SRB methods, seven strains deep-sea derived microorganisms (7 fungi) and eleven strain shallow-sea microorganisms (3 fungi and 8 actinomycetes) were screened out of twenty nine strains microorganisms isolated from deep-sea samples and one hundred and thirty three strains from shallow-sea, on the bioassay of brine shrimp and K562 cell lines.2 fungi and 3 actinomycetes with brine shrimp activity and 8 fungi and 5 actinomycetes with cytotoxicities were chosen based on the result of re-screening combining with HPLC and TLC chemical analysis. After choosing appropriate fermentation condition, c2b was fermented, and the broths of F-23-2 was also studied. The whole broths were extracted with ethyl acetate to give ferment extracts, which were subjected to silica gel column chromatography, Sephadex LH-20 and HPLC by bioassay-guided fractionation, respectively. Twenty compounds were isolated from the two active strains. Nine compounds (1-9) were isolated from fungus F-23-2 (Penicillium sp.), eleven compounds (10-20) from fungus c2b.By means of modern spectral analysis (UV, IR, NMR, MS, CD) and physico-chemical properties, the structures (see Table 1) of fifteen pure compounds were respectively determined. Among them there are four new compounds, including two new meleagrins (1, 2) and two new roquefortines (5, 6).In addition, the chemical structure types of compounds were involved in Meleagrin Alkaloids(1-4) and Roquefortine Alkaloids(5-8), Tryptophan derivates(9, 10), Benzene derivates(11), Steroides(12-14) and Esters(15).The anti-tumor activity in vitro against several cancer cell lines of these compounds was assayed by MTT or SRB methods. The results indicated that all of the compounds, seven compounds (1, 2, 3, 5, 7, 13,14) with anti-tumor activity were found. Compound 3 showed significant inhibition against A549 and median inhibition activity against HL60 (IC50 = 9.90 and 33.6μM respectively) Compounds 1, 2 5 and 7 showed median inhibition activity against A549 with IC50=62.5μM, 32.3μM, 84.5μM and 14.0μM, but all of them showed no inhibition activity against HL60. Compound 13 and 14 showed median cytotoxicity against tsFT210 with IC50= 89.5μM and 10.4μM. In addition, our study demonstrated for the first time that the Meleagrin and Roquefortine alkaloids showed inhibitory activity against A-549 and HL60.Summarily, this work obtained eighteen important active strains from marine-derived microorganism (seven stains from deep-sea and eleven strain from shallow-sea) and twenty compounds from two deep-sea derived active fungi. Among them, four compounds were identified new. Five compounds (1, 2, 3, 5, 7) with antitumor activities in vitro were discovered for the first time (they were three new compounds and two known ones). Studies mentioned above provided novel structures for searching leading antitumor compounds and strain resources of great value for further study and development of marine derived microorganism.
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