Studies On Bioactive Secondary Metabolites Of Marine-derived Fungi Penicillium Citrinum Y34

Marine microorganisms have unique genetic background and metabolic pathway due to their inhabiting in special ecological environment and complex interspecies relationship.Marine fungi,as the dominant group of marine microorganisms,can produce secondary metabolites with diverse structures and significant biological activities,and have become an important source of innovative drug discovery.Therefore,"to seek medicine from ocean"in the new century has become the consensus of governments and the goal of researchers.In this study,the bioactive secondary metabolites of marine derived fungi Penicillium citrinum Y34 were studied.Various chromatographies including silica gel column chromatography,reversed phase octadecylsilane（ODS）column chromatography,Sephadex LH20 column chromatography,and high performance liquid chromatography（HPLC）were used to separate the ethyl acetate（Et OAc）extract from the solid fermentation of marine fungus Penicillium citrinum Y34.A total of 51 compounds（1-51）were isolated,including 3 new compounds.Their structures were identified by UV,IR,MS,NMR,¹³C-NMR calculation,ECD and other spectroscopic methods.Theα-glucosidase inhibitory activities of the isolated compounds were evaluated in vitro.Results showed that 7 compounds including compounds 3,4,12,27,31,32and 47 exhibited potentα-glucosidase inhibitory activity with inhibition rates ranging from 49.0%to 99.2%at 400μM,better than that of the positive control acarbose.The IC₅₀ values of compounds 3,4 and 12 were 176.2,239.8 and 424.4μM,respectively.Compounds 3 and 4 exhibited non-competitive inhibition onα-glycosidase with Ki values of 212.7μM and 204.3μM,respectively.In addition,our study showed that 5compounds including compounds 2,27 and 31-33 exhibited significantly inhibitory activity against ATP-citrate lyase（ACL）with inhibition rates from 52.2%to 99.8%at20μM.The IC₅₀ values ranged from 1.54 to 17.45μM,showing great research prospect.In this study,we found that citrinamycin hadα-glucosidase and ACL inhibitory activities for the first time,and the structure-activity relationship ofα-glucosidase inhibitory activity of citrinamycin was also analyzed.Meanwhile,diphenyl ether and butyrolactones were also found to have good ACL inhibitory activity for the first time.The above research not only enriches the structural diversity of secondary metabolites from marine fungi,but also lay a solid foundation for the research and development ofα-glucosidase and ACL inhibitors.