| Comparing with terrestrial fungi,the fungi derived from deep-sea are more easily to product secondary metabiolites with unique structures,because of the extreme living environment.While,the cmpounds with special structres are especially important for the drugs to enhance the efficiency and specificity,reduce by-product and prevent drugresistant,which is scientific significant for discovering the lead compounds,studying the new target of drug action and the new mechanization,therefore,discovering the compounds of raw structures from the secondary metabiolism of deep-sea-derived fungi is one of the important method for searching the lead compounds.In order to search the compounds from deep-sea derived fungi with unique structures and bioactive as the drug lead compounds,In this thesis,33 strains deep-sea fungi were selected as screening objects,the experiment includes: Screening of target deep-sea fungus,the isolation and purification of target fungus,the identification of compounds,the biological active evaluation of compounds from target fungus.Firstly,four kinds of meadia are used to ferment the 33 strains deep-sea fungi in small scale,then using the detection methods of TLC,LC-MS and 1H-NMR to detect their crude extracts,besides,connecting the result of antitumor activity,finally,we selecte the Penicillium chrysogenum MCCC 3A00292 as study object.Then,through the large-scale fermentation,and using the isolation method: silica gel,ODS,Sephadex LH-20,HPLC to extract and insolate the crude extract.Finally,we identificate 16 compounds by NMR,ECD,CD,etc.in the isolation of three new versioltype analogues,namely peniciversiols A–C(1–3),and two novel lactone derivatives,namely penicilactones A and B(6 and 7),along with 11 known polyketides.The planar structures of the new compounds were determined by the comprehensive analyses of HRESIMS and NMR data,while their absolute configurations were resolved on the basis of comparisons of the experimental ECD spectra with the calculated ECD data.Compound 1 is the second example of versiols featuring a 2,3-dihydropyran-4-one ring.Additionally,compounds 6 and 7 are the first representatives of ?-lactone derivatives constructed by a 1,3-dihydroxy-5-methylbenzene unit esterifying with the ?-methyl-?-hydroxy-?-acetic acid ?,?-unsaturated-?-lactone moiety and ?-hydroxy-?-methyl-?-acetic acid ?,?-unsaturated-?-lactone unit.And the other 11 compounds are:decumbenone A(4),decumbenone B(5),3,3?-dihydroxy-5,5?-dimethyldiphenyl ether(8),Aspermutarubrol(9),3-hydroxy-5-(3-hydroxy-5-methylphenoxy)benzoic acid(10),3,4-dihydroxy-5-(3-hydroxy-5-methylphenoxy)benzoic acid(11),violaceol-?(12),3,8-dihydroxy-4-(2,3-dihydroxy-1-hydroxymethylpropyl)-1-methoxyxanthone(13),Asperdemin(14),Cyclopenol(15),radiclonic acid(16).Respectively,all of the isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines,including of BIU-87,ECA109,BEL-7402,PANC-1,and Hela-S3.Compound 1 exhibited a selective inhibitory effect against the BIU-87 cell line(IC50 = 10.21 ?M),while compounds 4,5,8 and 12-16 showed inhibitory activities against the ECA109,BIU-87 and BEL-7402 cell lines with the IC50 values ranging from 7.70 to 20 ?M. |
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