Study On The Secondary Metabolites From A Mangrove Endophytic Fungus

The ocean is the first place on the earth to breed life,occupying most of the e arth's area,and its special environment has created biological diversity.Mangrove pla nts living in coastal intertidal zone have special metabolic pathways because of their special environments such as high salinity and low oxygen content.They can metabo lize a large number of natural products with novel structure,rich types and diverse b iological activities,which provide rich chemical structures for the discovery of natural drugs,synthetic drugs and other new drugs?A large number of terpenoids with no vel structure and rich biological activity have been found in marine microorganisms,which also provide a large number of candidates for antitumor drugs and lead compo unds of antibiotics.In this thesis,the crude extract of mangrove fungus Talaromyces amestolkiae 30#had the activeinhibition of prostate cancer PC-3 cells?concentration 50?g/ml?,wit h the inhibition rate 85%.In order to find the secondary metabolites with anti-prostat e cancer bioactivity,this paper studied the secondary metabolites of this mangrove en dophytic fungus.A rice culture medium was used to culture endophyte Talaromyces amestolkiae 30#at room temperature..We obtained 25 compounds from the extracts of this fung us by using the silica gel column chromatography,ODS reverse column chromatograp hy,HPLC chromatography,et al.The chemical structure and absolute configuration of the compounds were determined by NMR,MS,HRMS,X-ray single crystal diffra ction,IR and other spectral data,combined with the analysis of optical rotation,CD and ECD.They were:four new compunds amestolkone A?1?,amestolkone B?2?,am estolkone C?3?,amestolkone D?4?,and with known 21 compunds,platensin SL1?5?,amestolkolides B?6?,aspergillumarins a?7?,aspergillumarins B?8?,talumarin a?9?,peniiso coumarins e?10?,5,6-dihydroxy-3-?4-hydroxypentyl?-isochroman-1-one?11??peniisocoumarin G?12??diaportinol?13??dichlorodiaportin?14??mucorisocoumar ins C?15??mucorisocoumarins A?16??5,6,8-Trihydroxy-4-?1?-hydroxyethyl?isocoum arin?17??sescandelin?18??sescandelin B?19??3-hydroxymethyl-6,8-dimethoxycoum arin?20??4-hydroxy-2-methoxyacetanilide?21??berkeleyamides C?22???3S,8a S?-3-be nzylhexahydro-2H-pyrido[1,2-a]pyrazin-1?6H?-one?23??2,5-dimethoxy-3,6-di?p-methoxyp heny1?-1,4-benzoquinone?24??a-methyl-paraconic acid?25?.In this thesis,we tested the inhibiton of compounds against prostate cancer cells?V-Ca P and PC-3 cells line?by MTT method.The results showed that compounds 2,6,and 14 had strong cytotoxic activity against PC-3 cells,with IC₅₀values of 25.34,8.24 and 12.37?M respectively;compounds 2,6 and 14 had strong cytotoxic activ ity against VCa P cells,with IC₅₀values of 15.68,10.95 and 20.35?M respectively.w e found that compounds 2 and 6 had a significant inhibitory effect on the migration of PC-3 cells by scratch wound assay.In addition,we also tested the antibacterial ac tivities of these compounds with five kinds of bacteria?Staphylococcus aureus,Escherichi a coli,Bacillus subtilis,Enterobacter cloacae,Enterococcus Faecium?by the 96 well plate m ethod.The results showed that compound 5,10,14,16 had inhibition against Staphyl ococcus aureus with moderate MIC value of 16?g/ml,and compound 14,16 had inhibi tion against Escherichia coli,with MIC value of 16?g/ml,respectively Compounds 1,5,10 and 22 had weak inhibition against Bacillus subtilis,with MIC value of 64?g/ml;compounds 9,14 and 16 had inhibition against Enterobacter cloacae,with MIC value o f 32?g/ml;compounds 9 also had inhibition against Enterococcus Faecium,with MIC v alue of 32?g/ml.