Two Marine Sources Of Microbial Secondary Metabolites Of Anti-tumor Active Ingredient

We have undertaken the screening for novel cell cycle inhibitors and apoptosis inducers from the marine-derived actinomycetes H2003 and Aspergillus terreus Thom by use of a mouse cdc2 mutant cell line, tsFT210. In anticipation of achieving the above objectives, marine-derived actinomycetes, H2003 and Aspergillus terreus Thom have been screened by using this model, the EtOAC extracts of strain H2003 and Aspergillus terreus Thom showed bioactivities of inhibiting the cell cycle progression and cytoclasis of tsF210 cells. Thus, we selected them for further investigation.Eleven compounds were isolated from the bioactive part, EtOAC extract of strain H2003, by repeated column chromatography on Sephadex LH-20, silica gel and RP18, followed by reverse-phase high performance liquid chromatragraphy. The structures of compounds were elucidated mainly by use of spectroscopic method (UV, IR, MS, 1D-NMR, 2D-NMR) and according to their physicochemical properties: dibutyl phthalate (1); Acetic acid 4-acetoxy-buta-l,3-dienyl ester (2); 3,4-Dihydroxy-2-methylpyridine (3); 4-hydroxybenzoic acid (5); Protocatechuic acid methyl ester (6); cyclo-(Pro-Ile) (7); cyclo-(Pro-Leu) (8); cycol-(Pro-Val) (9); 4,4'-Dintrobibenzyln (10) ;cyclo-(Pro-Phe) (11); cyclo-(Pro-Ala) (12); cyclo-(Ala-Val) (13); N-(4-hydroxyphenethyl)acetamide (14); cyclo-(4-hydroxy-Pro-Leu) (15); cyclo- (Ala-Ile) (16) ; cyclo-(Ala-Leu) (17); cyclo-(Val-Leu) (18); cyclo-(Tyr-Pro) (19); cyclo-(Gly-Phe) (20); cyclo-(Ala-Phe) (21); cycol-(Gly-Pro) (22). The structure of compound (4) is still in affirming.By the same activity-guided method, thirteen compounds were isolated from the bioactive part, EtOAC extract of Aspergillus terreus Thom, by physicochemical evidence and spectroscopic methods, the structures of the eleven compounds were elucidated as: ergosterol (23); glyceride (24); chrysophanol (25); emodin (26); 1,8-dihydroxy-3-(hydroxymethyl)anthracene-9,10-dione (27); benzoic acid (28); diisobutyl phthalate (29); 3,4-dimethoxyphenol (30); dithiol gliotoxin (31); 3-methoxyphenol (32); 2-(4-hydroxyphenyl)acetonitrile (33);(E)-N-(4-hydroxystyryI)formamide (34); (Z)-N-(4-hydroxystyryl)formamide (35).Bioassay results indicated that 1,23,24,26,29,30,32 show cell cycle inhibition and cytoclasis of tsFT210 cells. Compound 14,34 showed a strong apoptosis of tsFT210 cells. Compound 3,4,5,11,25 show cell cycle inhibition of tsFT210 cells.Bioassay results indicated that we isolated the main antitumor active compounds of strain H2003 and Aspergillus terreus Thorn successfully which showed that this antitumor model and the method were exact and available in achieving bioactive components from marine microbes.