The Secondary Motabolites Of Azaphilones From The Fungus Talaromyces Aculeatus And Their Bioactivities

Due to the worsening of the human environment, frequently accured of a number of incurable diseases that threat to human life and health, the development and research of pharmaceutical microbial resources is becoming more and more attention. Because of the special environment, fungi can display unique in molecular mechanism of gene, enzyme properties, metabolic regulation and so on. According to the report, fungus growing in special environment has a broad prospect in terms of new drug, new kind enzyme drug and new healthy food research and development and the like. In this paper, structure and biological activity of secondary metabolites of the fungus from saline sources are research. The research content mainly includes isolation and screening of bioactive fungis, separation and purification of secondary metabolites and structural elucidation, biological active of monomer compounds.33 fungal strains were isolated from 3 samples, including Guangxi Fangchenggang stone door Island, saline soil and dam of Heze. Then we screened a strain of saline alkali soil fungus Talaromyces aculeatus DS-62013 as the research object of this thesis, through small scale fermentation. By using solvent extraction, silica gel column, Sephadex LH-20, ODS, semi-preparative HPLC and other separation means, NMR, IR, UV, MS, CD spectroscopic techniques, 20 compounds(1–20) were isolated from fungus Talaromyces aculeatus, 11 of them are new compounds(1-11), and compounds(2-15) were asazaphilones. In terms of configuration, we use NOESY, ECD, and VCD to speculate on the absolute configuration of azaphilones compounds(2-9).In this study, parts of the isolated compounds were evaluated for their cytotoxic activities against five common human tumor cell lines using the previously reported MTT assay. From the assay, compound 12 have some inhibitory activity against leukemia cells HL-60 with IC50 values of 19.3 ?M; compound 13 have some inhibitory activity against liver cancer cells SMMC-7721 with IC50 values of 10.9 ?M. By micro-dilution method to determining the antibacterial activity of the compounds, compared with compounds 9, 15(MIC, 1.56 ?M) and positive control drug ciprofloxacin(MIC, 0.625 ?M), they exhibited similar antibacterial activities against V. anguillarum. New compounds 3-9 were tested for inhibitory activity screening of ?-glucosidase in vitro. The results show that, compounds 3 and 9 showed some inhibitory activity to ?-glucosidase with IC50 values of 234.9, 22.9 ?M, and are thus more potent than the positive control, acarbose(101.4 ?M), miglitol(5099.7 ?M) and 1-Deoxynojirimycin(78.6 ?M).In conclusion, this present study we isolated natural products with good activity from Talaromyces aculeatus, and we use of ECD, VCD and quantum chemical calculations methods to determine the their absolute configuration. Activity screening indicated that some compounds have good antimicrobial and cytotoxic, and Compound 9 has a strong inhibitory activity for ?-glucosidase, this provides a basis for the development and application of pharmaceutical lead compounds.