Studies On The Antitumor Constituents Of Streptomyces Flavorectus Z₄-007

We have undertaken the screening for novel cell cycle inhibitors and apoptosis inducers from the marine microorganisms by use of a mouse cdcl mutant cell line, tsFT210. In anticipation of achieving the above objectives, the metabolites of Streptomyces flavorectus Z4-007 have been screened by using this model and their EtoAc extract showed bioactivity of inhibiting the cell cycle progression and inducing apoptosis of tsF210 cells. Thus, we selected it for further investigation.Streptomyces jlavorectus Z4-007 was isolated from Jiaozhou Bay. The fermentation broth of the stain was successively partitioned with EtoAc and n-butanol to yield crude extracts. From the bioactive part, EtoAc extract, eight compounds 1~8 were isolated by column chromatography on, Sephadex LH-20, Silica VLC and RP18, followed by reverse-phase high performance liquid chromatragraphy and recrystalization . The structures of eight compounds 1-8 were elucidated mainly by use of spectroscopic method (UV, IR, MS, 1D-NMR, 2D-NMR) and according to their physicochemical properties: l-(2,4-Dihydroxy-3,5-dimethyl-phenyl) -hexa-(E,E) -2,4-dien-l-one (1); 2-Acetylamino-3-hydroxy-4-methyl-benzoic acid (6); 6-Hydroxy -2 -methyl-hept-2-enoic acid 7-hydroxy-3,9-dimethyl-2-oxo-oxonan-4-yl ester(7); Benzo[d]isoxazol-3-one(8); the estimated stucture of compound 3 was Actinomycin Au7b, and compound 2, 3, 4 is a series of actinomycins, their structure are still inducing. Compound 5 was isolated from compoud 3 when it was put in the light for some time.Bioassay results indicated that compound 1 showed a strong bioactivity in inhibiting the cell progression at the GO/1 phase of tsFT210 cells with the value of l00ug/ml and at the G2/M phase of tsFt210 cells with the value of 50ug/ml; compound 2,3,4 show a strong activity of inducing apoptosis on mouse tsFt210 cells, especially compoud 3 inhibited the cell progression at the GO/1 phase of tsFT210 cells with the value of lug/ml. They are the main anti tumor active compounds of thisstrain.In summary, compounds 1, 2, 3, 4, 5, 6, 7, 8 were isolated for the first time from Streptomyceflavorectus. and compound 7 is a new compound. The inhibitory activity on cell cycle of compound 1, were also discovered for the first time.