Study On The Bioactive Constituents From Sponge-Derived Bacterium 041381 And Actinomyces Sh6004

Because of the special ecological environment, marine-derived microorganisms possess distinct and complex metabolic capabilities, resulting in wide diversity of their secondary metabolites in chemical structure and biological activity. Thus, bacterium and actinomyces become important resources of active lead compounds. This thesis describes the bioactive constituents from sponge-derived bacterium 041381 and actinomyces sh6004. The work includes screening aimed strains, fermentation studies, bioassay-guided fractionation, structural elucidation, preliminary evaluation for antibacterial activities of pure compounds, synthesizing compound 1 and determining its absolute configuration.After choosing appropriate fermentation condition, large-scale fermentation and preparation of the active fractions were performed to obtain the active components from the bioactive strains. By means of column chromatography over silica gel, Sephadex LH-20, preparative TLC and semi-preparative HPLC, 14 and 6 compounds were isolated from marine derived bacterium 041381 and actinomyces sh6004 brothes, respectively. The separation procedure is guided by disk diffusion method. By analyzing physico-chemical properties and spectral analysis (IR, UV, MS, NMR, etc.), their structures were elucidated as 2-(heptan-3-yl)quinazolin-4(3H)-one (1), 2-(heptan-3-yl)-2,3-dihydroquinazolin-4(1H)-one (2), 2-methylquinazolin-4(3H)-one (3), 2?benzylquinazolin-4(3H)-one (4), cyclo-(Pro-Ile) (5), Cyclo-(Pro-Leu) (6), Cyclo-(Pro-Val) (7), Cyclo-(Pro-Phe) (8), Cyclo-(Tyr-Pro) (9), Campester (10), Ergosterol(11), Ergosterol peroxide(12), benzamide (13), 2-phenylacetic acid (14), bisdethiobis-(methylthio)-gliotoxin (15), actinomycin D (16), actinomycin C2a (17), actinomycin C3 (18). The identified obtained compounds include four quinazolinone alkaloids (1-4), five dicyclopeptides (5-9), three sterols (10-12), two benzene derivates (9-13) and four other alkaloids (14-18). Compounds 1 and 2 were new compounds.Compound 1 was synthesized, and its absolute configuration was determined .Meanwhile two by-products were obtained as enantiomers.The antibacterial activity against several bacteriums of these compounds was assayed by disk diffusion method and among them 6 compounds (1, 2, 15-18) with antibacterial activity were found. Compound 1 and 2 show high inhibition activity against Candidaalbicans. Compounds 15-18 show high inhibition activity against Staphylococcus aureus and Bacillus subtilis. In addition, our study demonstrated for the first time that the quinazolinone alkaloids show inhibitory activity again Candidaalbican .