Studies On Secondary Metabolites Of Three Fungus Derived From Mangrove And Their Anti-tumor Activity

Due to the unique living conditions, microorganisms derived from mangrove environments possess special hereditary and physiological character, and have the capability to produce special secondary metabolites with unique skeletons and bioactivities. By antitumor bioassay screening,20 microorganisms of the 223 isolated mangrove derived ones were chosen. By chemical analysis,3 fungi of the 20 bioactive strains were chosen to further research for their active component. This study include the screening of microbial strains, selection of working strains, optimization of culture conditions, bioassay-guided fractionation, structural determination and testing for anti-tumor activities of pure compounds.The 97 microorganism strains, including 58 fungi and 37 actinomycetes were isolated from the rhizosphere soil of the mangrove grown in Guangxi and Hainan Province of China. Using antitumor bioassay testing,20 bioactive strains were positive.3 fungi (ZHN7-08, ZHN1-09, ZHN2-20) were selected for further study for the component of secondary metabolites after HPLC analysis for the 20 active strains. The fermentation conditions were determined after a series of experiment about bioassay testing and HPLC analysis.Seven new compounds, including five drimane sesquiterpenoids, one cytochalasin and one lovastatin, as well as one new natural product (drimane sesquiterpenoid), together with 30 known ones were isolated from the EtOAC extracts of the fermentations chromatographed by repeated TLC, silica gel column, Sephadex LH-20 and semi-preparative HPLC. Their structures were determined by means of physico-chemical properties and spectral analysis.The antitumor activities against several cancer cell lines of these compounds were assayed. Results are as follows, compound 16 and 19 showed week cytotoxicity, new compound 4 showed moderate cytotoxicity, and compound 23 showed moderate cytotoxicity on P388 cell line, also compound 23 showed strong cytotoxicity on A549 cell lines.In summary,38 compounds including 7 new structures and 1 new natural product were isolated from fermentations of the three fungi. One of them showed (new compound 23) significant cytotoxicity. Achievement are as follows:Novel structure types are provided, four compounds with antitumor activity were provided, drug-producing strains were provided.