| Due to the special environment, chemical novelty and diversity of biological activities of metabolites from marine-derived microorganism made a prominent contribution to the new lead compounds. In order to search for new bioactive compounds, a study on microorganism from different marine origins was carried out. Studies include purification and structural elucidation of the secondary metabolites, preliminary evaluation for bioactivities of pure compounds.In all, 77 compounds were separated and purified, from the bioactive extracts of the 5 aimed strains, by means of solvent extraction, silica gel column, Sephadex LH20, ODS-C18, PHPLC, and etc. From fungus Aspergillus taichungensis ZHN-7-07, 23 compounds (1-23) were isolated; from fungus Aspergillus versicolor CXCTD-06-6a, 19 compounds (24-42) were isolated; from fungus CTD-13C, 16 compounds (20, 43-57) were isolated; from fungus ZLN-20-03, 7 compounds (58-64) were isolated; from bacterium Aeromonas sp.CB101, 13 compounds (65-77) were isolated.Basing on their physico-chemical properties and spectral data (IR, UV, MS, NMR, CD, and X-ray), combined with conformational analysis and marfey's mothod, structures of the 77 compounds were respectively determined. Among them there are 15 polyhydroxy-p-terphenyls (1-15), 34 alkaloids (16-23, 30-35, 43-44, 48-50, 58-61, 65-73, 74-75), 9 polyketides (24-27, 28-29, 45-47), 12 benzol derivatives (36-37, 40, 51-54, 62-64, 76-77), 2 sesquiterpene (38, 39), 1 steroids (42), 4 other structural type compounds (41, 55-57). Twenty-two compounds are new, including 6 polyhydroxy-p-terphenyls (1-2, 4, 11-13) with a prenyl side chain, 1 polyhydroxy-p-terphenyl (5), 1 indole diketopiperazine dimmer (21) with a rare connection of N1-C6, 1 stephacidin alkaloid (23) with a rare trans- relative configuration of C6-C7 to C4-N24, 5 new indole diketopiperazine alkaloids (16-18, 32-33), 3 new xanthones (25-27), 3 new indole alkaloids (65-67), 1 amide alkaloid (44), 1 sesquiterpene (39). In the study, we established the relative and absolute configurations of indole diketopiperazine alkaloids (16-18, 21, 23, and 32-33) by the combination of NOESY, X-Ray, CD, and Marfy's method. We determined the relative and absolute configurations of xanthones (25-27) by the combination of biosynthetic origin, coupling constants, optical rotations and conformational analysis.With the purpose of looking for the potential therapeutical effect of the compounds isolated, the assays of antitumor, anti-inflammatory, anti-virus, antioxidation, and antibiotic activities were applied. Fourty-three compounds were evaluated for their cytotoxicities against several cancer cell lines such as P-388, HL-60, A-549, BEL-7402, and etc., by the MTT or SRB methods. Among them, 8 new compouds showed different levels of cytotoxicities. Compound 3 and new compounds 1, 2, 4, 5, 11-13, and 23 exhibited significant inhibitory activities against HL-60, A-549, P-388 cell lines. The IC50 values of compound 1 against HL-60, compounds 3, 5, and 12 against P-388 were 1.53, 1.99, 2.70, and 1.57μM, respectively. The known compound 24 showed moderate cytotoxicities against the A-549 and HL-60 cell lines with the IC50 values of 3.86 and 5.32μM, respectively, while compounds (25-27), three new analogus of 24, showed no cytotoxicities on these two cancer cell lines. This result had a significant implication that the double bond between C-3'and C-4'was an essential pharmacophoric moiety in sterigmatocystins, and the saturation of it would lead to the absence of cytoxicity. In RAW264.7 cells, compound 45 could inhibit the secretion of TNF-α, the expression of TNF-αmRNA and the translocation and activation of NF-κB; inhibition of NF-κB and MAPK activation could affect semivioxanthin (45) mediated TNF-α, (CD)80, CD86 and MHC II expression. These result suggested that compound 45 exhibited significant anti-inflammatory activity.Summarily, this work obtained 77 compounds, including 22 new compounds and 2 new natural products, from five active marine-derived microorganisms. New compouds 1, 2, 4, and 11-13 were polyhydroxy-p-terphenyls with a prenyl side chain; new compound 21 was an indole diketopiperazine dimmer with a rare connection of N1-C6; compound 22 and new compound 23 were two stephacidin alkaloids with a rare anti- relative configuration of C6-C7 to C4-N24. Fourty-three compounds were evaluated for their antitumor activities, eight of which showed significant activities. Anti-inflammatory activities of compound 45 were reported. This study provides novel structure types for marine natural product chemistry and bioactive template compounds for exploring new antitumor and anti-inflammatory drugs.
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