Study On Secondary Metabolites And Biological Activities Of Penicillium Expansum GY618

Objective:In this thesis,the secondary metabolites of solid fermentation of Penicillium expansum GY618 were studied.The structures of the secondary metabolites were characterized,and the antibacterial and antitumor activities of the compounds were evaluated to find natural products with good activities.Methods:The rice solid fermentation product of the target strain was extracted by ethanol.Then the total paste was dispersed with water and extracted by ethyl acetate.The pure compounds were obtained by silica gel column chromatography,thin layer chromatography,reverse phase ODS column chromatography,Sephadex LH-20 gel column chromatography,and semi-preparative HPLC column chromatography.Then mass spectrometry,nuclear magnetic resonance spectroscopy,infrared spectroscopy,ultraviolet spectroscopy and other spectral methods as well as the physicochemical properties of the compounds were used to elucidate the structure of all compounds.The compounds were also tested against Staphylococcus aureus,Monilia albican,Escherichia coli and Pseudomonas aeruginosa assay and anti-lymphoma cell U937assay.Results:Twenty compounds（1-20）were isolated from Penicillium expansum GY618,including heteroterpenoids,polyketones,quinones,sesquiterpenoids,alkaloids,and steroids.Among them,there are 5 new compounds and 15 known compounds.Among the new compounds,1 is a new heteroterpenoid compound.2 is a new polyketide compound.3 and 4 are new quinones.5 is a new sesquiterpenoid.Compound 6 and 7 are sesquiterpenoids.8 is polyketide compound.9-11 are alkaloids.12-20 are steroid compounds.The configurations of 1,2 and some other compounds were determined by 1D,2D NMR,UV,IR and ECD methods simultaneously combined with the literatures.The antibacterial and antitumor biological activities of some monomer compounds were evaluated.In the antibacterial experiment,compounds 5 and 17showed certain antibacterial effect against P.aeruginosa（MIC=62.5μg/m L）,compounds 4 and 12-14 showed moderate antibacterial effect against P.aeruginosa（MIC=125μg/m L）.Other compounds showed little or no inhibitory effect against P.aeruginosa（MIC>250μg/m L）.Compound 5 had a certain inhibitory effect on E.coli（MIC=62.5μg/mL）,and compound 13-14 and 17-18 had an average inhibitory effect on E.coli（MIC=125μg/m L）.Other compounds showed little or no inhibitory effect against E.coli（MIC>250μg/m L）.All compounds showed little or no inhibitory effect against S.aureus（MIC>250μg/m L）.Compounds 2 and 8 had certain inhibitory effect on C.albicans（MIC=62.5μg/m L）,compound 5 had moderate inhibitory effect on C.albicans（MIC=125μg/m L）,and other compounds had weak or no inhibitory effect on C.albicans（MIC>250μg/m L）.The antilymphomatocyte U937 activity was determined by the inhibition rate of the compound incubated at 50μM for 72 h.Compound 11 showed a weak inhibitory effect on tumor proliferation,with an inhibitory rate of 69.2%at 50μM(IC₅₀43.1±0.7μM).Conclusion:The fermentation products of Penicillium expansum GY618 were extracted by silica gel column chromatography,thin layer chromatography,reversed phase ODS column chromatography,Sephadex LH-20 gel column chromatography and semi-preparative HPLC chromatography.Five new compounds and 15 known compounds were isolated,including heteriterpenoids,polyketones,alkaloids,sesquiterpenoids,quinones and steroids.Compounds 5 and 17 had certain bacteriostatic effect on Pseudomonas aeruginosa.Compound 5 has certain bacteriostatic effect on Escherichia coli.All compounds had weak or no inhibitory effect on S.aureus.Compounds 2 and 8 had certain antibacterial effect on Candida albicans.The proliferation inhibition of lymphoma cells U937 was determined by the inhibition rate of the compound incubated at 50μM for 72 h.Compound 11 showed weak tumor inhibitory activity with an inhibitory rate of 69.2%at 50μM(IC₅₀43.1±0.7μM).