Studies On Bioactive Components From The Secondary Metabolites Of Two Actinomycetes

Actinomyces are widely distributed in nature in a variety of habitats, they are of characterize of large quantity and are the main producer of antibiotics and other bioactive substance. Among more than 30,000 bioactive nature products found from the secondary metaboilites of microbe, two-thirds derived from actinomycetes. Therefore, it is of significance to find novel active leading compounds from the actinomycetes.In this thesis, with the application of chemical screening (TLC) and antimicrobial activity screening method, two target strains YIM PH20352 and YIM PH20520, which secondary metaboilites are rich in chemical composition and good activity, were selected from 30 strains of soil actinomycetes for the following bioactive secondary metabolites research. On the basis of morphological characteristics and the 16S rRNA gene sequences, strains YIM PH20352 and YIM PH20520 were identified as Streptomyces cellulosae and Amycolatopsis speibonae respectively.With the practice of silica gel column chromatography, gel chromatography on Sephadex LH-20, and HPLC chromatographic technology,5 compounds were isolated and purificated from strain YIM PH20352, and chemical structures of these 5 compounds were elucidated by their mass (MS) and nuclear magnetic resonance (NMR) spectroscopy. They respectively are:Rabelomycin (1), Urdamycinone B (2), Dehydrorabelomycin (3), Dehydroxyaquayamycin (4) and 5,12-Naphthacenedione (5); 7 compounds were isolated and purificated from strain YIM PH20520 and chemical structures of these 7 compounds were elucidated by their mass (MS) and nuclear magnetic resonance (NMR) spectroscopy. They respectively are:Echinosporin (6),7-deoxyechinosporin (7), Hexahydro-3-(phenylmethyl)pyrrolo[1,2-a]pyrazine-1,4-dione (8).2,5-Piperazinedione,3-(2-me1hylpropyl)-6-(phenylmethyl) (9), Pyrrolo[1,2-a]pyrazine-3-acetamide, octahydro-1,4-dioxo (10), 3-Benzylpiperazine-2,5-dione (11) and Pyrrole-2-carboxylic acid (12).Antibacterial and antitumor bioactivity assay were performed on compounds 1-12 respectively, among them, compound 1 showed obvious inhibition activity against the Staphylococcus aureus and Bacillus subtilis with the same MIC values of 8μg/mL; compound 3 showed inhibition activity against the Aspergillus niger, Fusarium oxysporum and Fusarium solaniwith the MIC values of 64,64 and 128 μg/mL; compound 6 showed very stronger anticancer activity against HCT116, Hela, BGC-823 and HepG-2 cells with the IC50 values of 2.23,3.23,3.72 and 3.93 ug/mL; compound 7 exhibited the stronger cytotoxicity against HCT116 cell with the IC50 values of 8.56μg/mL; compound 8 showed very evident inhibition activity against Canidia Albican with the MIC values of 2μg/mL.