Studies On The Secondary Metabolites And Bioactivities Of Guignardia Mangiferae And Fusarium Solani

This dissertation is divided into three chapters.The chapters 1 and 2 described the chemical and bioactive constituents on metabolites of Guignardia mangiferae from Dendrobium nobile leaves and Fusarium solani from leaves of Liriodendron chinense,respectively.The third chapter mainly was a review with regard to the research progress of meroterpenoids produced by fungi reported in the literature over the past 70 years.By means of chromatography on a silica gel column,Sephadex LH-20,ODS C-18 reversed phase column,semi-preparative HPLC and other separation techniques,71 compounds,including 23 new ones were isolated and identified from the endophytic fungi of the two plant metabolites.And their structures were determined by NMR analysis,HRESIMS,infrared and ultraviolet spectra analysis,quantum chemical calculations,X-ray single crystal diffraction analysis,Mosher reaction,Mo₂?OAc?₄ reagent,and other modern means.The main structural types of compounds included meroterpenoids,polyketides,and authraquinones,and so on.From the rice fermented by Guignardia mangiferae,the main compounds of meroterpenoids were isolated,which consisted of 11 new skeleton compounds of meroterpenoids with a spiro ring system.They mainly related new spirocyclic skeletons for monoterpene-shikimate-conjugated meroterpenoids,a new spirocyclic skeleton formed by shikimate and ring-opening monoterpene,and new spirocyclic skeletons for sesquiterpene-shikimate-conjugated meroterpenoids.There were also 10 new meroterpenoids.All of meroterpenoids were derived from terpene-shikimate mixed.Targets of novel compounds were predicted by computer-reverse virtual and 2D pharmacophore fingerprinting to obtain the target with a highest overall score of 11?-HSD1,and the highest scoring compound 1 was docked with 11?-HSD1.Subsequently,the binding of 11?-HSD1 to compound 1 was evaluated by MST in vitro and its inhibitory activity against 11?-HSD1 was researched.Furthermore,we researched compound 1 targeting 11?-HSD1 inhibitory activity in HepG2 cells and the inhibitory effect of compound 1 on the differentiation of 3T3L-1preadipocytes,respectively.Compound 1 targeting 11?-HSD1 inhibitory activity was validated in vitro.Polyketides and authraquinones were isolated from rice fermentations of Fusarium solani,which contained a new skeleton polyketide possessing a pentaleno[1,2-c]pyran moiety and a new steride with A and B rings degraded.We tested the tumor cytotoxic activities and cyclooxygenase-2?COX-2?enzyme inhibitory activities on these two new compounds.