Studies On The Bioactive Constituents Of Marine-derived Actinomycete B2202

The occurrence of cancer are closely related to the regulation of cell cycle and apoptosis. Therefore, novel inhibitors of the cell cycle or inducers of apoptosis would be good candidate for cancer chemotherapy. From this viewpoint, we have undertaken the screening for novel cell cycle inhibitors and apoptosis inducers from the marine microbe by use of mouse cdc2 mutant cell line, tsFT210 . In anticipation of achieving the above objects, 30 marine-derived strains have been screened using this model and the methanol-water extracts of marine-derived actinomycete B2202 showed stronger bioactivity of inducing the apoptosis and cytoclasis of tsFT210 cells. Thus, it was selected for further investigation.The acetone-water extract of actinomycete B2202 was successively partitioned with EtoAC and n-BuOH to yield crude extracts. From the bioactive part, EtoAC extract, four compounds 1~4 were isolated by silica gel, Sephadex LH-20 and reverse-phase high performance liquid chromatragraphy. The structure of four compounds were elucidated mainly by use of spectroscopic methods (UV, IR, MS, 1D-NMR, 2D-NMR). n-BuOH extract, eight compounds 5-12 were isolated by above methods and elucidated mainly by use of spectroscopic methods (UV, IR, MS, 1D-NMR, 2D-NMR) .The antitumor activities of compounds 1-12 were assayed by SRB and flow cytometry using mammiferous cancer cell lines of tsFT210 .Among them, compound 1, 5, 8 could inhibit the cell cycle at different phase; compound 2, 9,10 showed strong apoptosis inducing activity; compound 4, 7,12 could inhibit the cell cycle at different phase and showed strong apoptosis inducing activity; compound 11 could inhibit the proliferation of tsFT210.Compound 2 is new and compound 6 is found from marine microbe and its strong activity is said first time in this paper. The activities of compound 4, 6~10 were reported firstly in this paper.