The Studying On The Antitumor Active Components Of Marine Fungus H1-04

We have undertaken the screening for novel cell cycle inhibitors, apoptosis inducer and cytotoxic activity from the secondary metabolites of marine fungus HI-04 by use of a mouse cdc2 mutant cell line, tsFT210. The secondary metabolites of marine fungus HI-04 were successively partitioned with efficient Hexane and CHCls to yield crude active extracts. Successive purification of the active parts by silica gel, Sephadex LH-20, ODS, followed by reverse-phase high performance liquid chromatography and recrystalization, led to the isolation of six compounds 1-6.The structures of six compounds 1~6 were elucidated mainly by use of spectroscopic method (UV, IR, MS, 1D-NMR, 2D-NMR) and according to their physicochemical properties: 4,8-dihydroxy-l-tetralone,isosclerone (1), Terreperoxime (2), 7-Hydroxy-12-methyl-l,11-bis-methylsulfanyl- 9-oxa-12, 14-diaza-tricyclo[9.2.2.03, 8] pentadeca-3,5-diene-13,15-dione (3), Cyclo(tryptophany lprolyl)Hexahydro-3-(lH-indol -3-ylmethyl)pyrrolo[l,2-a]pyrazine-l,4-dione (4), 5H,14H-Pyrrolo[l",2": 4',5']pyrazino [1 ',2': 1,6]pyrido[3,4-b]indole-5,14-dione, 1,2,3,11,12,14a-hexahydro-12-(2-methyl-propenyl) (5), Imine derivative (6).Bioassay results using FCM and SRB indicated that compound 1, 2, 6 showed a strong bioactivity in apoptosis inducing and cytotoxic activity on tsFT210 cell. They are the main anticancer active compounds of HI-04. Compound 3 showed a tender bioactivity in apoptosis inducing and cytotoxic activity on tsFT210 cell. Compound 5 showed a strong bioactivity in inhibiting the cell progress at the S phase of tsFT210 cell.In summary, compounds 2, 3 and 6 were novel compounds. The activities ofcompound 2,3 and 6 were also discovered for the first time.