| The unique natural environment and geographical location of the two Polar Regions lead to great differences,uniqueness and richness of microbial resources in there.In order to adapt to the harsh living environment,polar microorganisms had formed unique molecular mechanisms and physiological and biochemical characteristics in the process of evolution,including genome composition,gene express regulation and metabolic regulation,resulting in important and unique metabolites of polar microorganisms.Therefore,the Arctic and Antarctic regions are considered as potential and important extreme microbial resource pools,as well as important sources of producing new active molecules for medicinal purposes,providing a new perspective for natural drug research and development.In the early stage of our research,when Eutypella sp.D-1 from the Arctic was fermented on PDB medium,the fungus grew fast and lots of crude extract of the fermentation broth were obtained.After systematic isolation and structure elucidation,a series of new diterpenoids and cytochalasins were identified as the fermentation products.Because of the strong cytotoxic activities of the diterpenoids,more new diterpenoids containing characteristic "cyclopropyl" groups were isolated by fermentation in directional optimized medium based on OSMAC strategy.In this study,we hope to obtain more different novel secondary metabolites by changing the composition of the medium.Based on the HPLC and cytotoxicity results,rice solid medium was chose to be the fermentation medium of fungus Eutypella sp.D-1.Eleven compounds were separated from the fermentation broth of ethyl acetate extraction of fungus Eutypella sp.D-1 by solvent fractionation extraction,decompressing phase chromatography,medium pressure column chromatography on ODS and silica gel,and HPLC.These compounds were identified by IR,UV,1D NMR,2D NMR,HRESIMS,and ESIMS.These 11 compounds were determined as follows: eutypellacytosporin A(1),eutypellacytosporin B(2),eutypellacytosporin C(3),eutypellacytosporin D(4),cytosporin D(5),cytosporin F(6),cytosporin G(7),cytosporin H(8),cytosporin I(9),cytosporin J(10),cytosporin K(11).Among them,compounds 1?4 are new compounds.Compounds 1?4 are cytosporin and decipienolide,which are linked by O-atom to form new compounds.The absolute configuration of the new compounds is determined by modified Mosher method.The cytotoxic result of all the isolated compounds showed that only compounds 1?4 had moderate cytotoxicities to human prostate cancer cell DU145,human pancreatic cancer cell PANC-1,human pancreatic cancer cell SW1990 and human hepatocellular carcinoma cell Huh7.Their IC50 values ranged from 4.9 to 17.1 ?M,and compounds 5?11 showed no cytotoxicity.In general,in this paper,the chemical constituents of the fermentation products of polar fungus Eutypella sp.D-1 were studied by using various modern chromatographic separation techniques,and new active compounds were found.This results can provide important basis for rational and effective utilization of polar microbial resources in China,and have important strategic significance for deep recognizing the potentials of polar medicinal microbial resources and researching and developing polar microbial medicinal resources.The structure of compounds 1?11 are as follow:... |
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