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

Ocean with high pressure, high salt, hypoxia, cold, oligotrophic and other uniqueenvironmental characteristics, in which marine-derived microorganisms can producenovel bioactive secondary metabolites through their unique metabolic pathways, hasbecome the great important resource for natural products research. The south ChinaSea whose the deepest part is more than5500meters is located in the tropical andsubtropical areas and is the largest marginal sea in the western Pacific Ocean. As itcontains a great number of microbial resources, more and more countries payattention to the research of it. In order to study furtherly the medicinal value ofmicroorganism in the south China sea, this article carries out the isolation andcultivation of the fungus from the south China Sea, studies its secondary metabolitesand their anti-tumor activity.106fungal strains were isolated from25sediment samples from the South ChinaSea. By antitumor bioassay screening,19active strains were chosen. Combined withTLC and HPLC, chemical analyses were performed for the active secondarycompounds of these19strains, and3fungi were selected for further study.Followed the Large-scale fermentations, the EtOAC extract of the three bioactivestrains were chromatographed by Sephadex LH20, repeated silica gel column,preparative TLC and semi-preparative HPLC, which lead to the isolation of thirty-twocompounds（1-32），six compounds（33-38）and six compounds（39-44）from thesouth China sea derived fungi XJW-56(Aspergillus sclerotiorum), XJW-105(Penicillium brocae), and XJW-160(Penicillium citrinum), respectively.Nine new compounds, including asterriquinones (1-3), cyclic tripeptide (11),pyrazine alkaloids (18-19), one other compound（25），and indole alkaloids (33-34)were determined based on the physico-chemical properties and spectral data (IR, UV, MS, NMR, etc.), togethe with35known compounds, identified as sevenasterriquinones (4-10), six cyclic tripeptide (12-17), two pyrazine alkaloids (20-21),eight derivatives of benzene (22-24，28-30,38,43), two xanthones (31-32)，fivealkaloids（27，35-37,44），four citrinin compounds（39-42）and one other compound（26）。32compounds including6new structures (1-3、11、18-19) were isolated fromfermentations of fungi XJW-56. The antitumor activities against several cancer celllines of compounds (1-10) were assayed. Results are as follows, compound2,3and7-10showed week cytotoxicity, with IC5072.18,83.07,35.34,31.50,42.99and9.99μ mol/L respectively.6compounds including2new structures (33-34) were isolatedfrom fermentations of fungi XJW-105. The secondary metabolites of the strain ofthe antitumor activity remain to be determined.6compounds were isolated fromfermentations of fungi XJW-160. The antitumor activities against several cancer celllines of compounds (39-44) were assayed. None of them had antitumor activity.In sumary,106gungi were isolated from25sediment samples from the SouthChina Sea. We studied the secondary metabolites of three srains of those and gained44compounds including eight new compounds, six compounds with differentantitumor activity. The research laid a solid foundation to explore the South China Seamicrobes antitumor active ingredient and its potential medicinal value.