Study On The Secondary Metabolites And Their Activities From Four Specific Environment Fungi

Natural products have rich skeleton types and a wide range of biological activities,and the separation of active compounds with potential medicinal value is the key to develop innovative drugs.Fungi are one of the important sources of natural drugs,and the research of secondary metabolites has been a hot topic of natural medicinal chemistry.Fungi have a high"creation coefficient"of metabolites.fungal resources in special environment such as low temperature,ocean,plant endogenous,animal sharing and epiphytic fungi have different metabolic pathways and defense systems,and have a higher probability to produce a series of functions with novel structure and rich bioactive metabolites.The discovery of drug lead molecules from the natural products of special border fungi is of great strategic significance for creating new drugs with independent intellectual property rights.In this study,75 fungi were isolated from seven animal samples(including one terrestrial insect and six marine animals).Small-scale fermentation was performed for all of the fungi.Four animal-derived fungi(three from this experiment and one Marine animal from the fungal library)were finally selected to systematically study the chemical composition of the fermentation products,by HPLC-DAD-UV and the results of small-scale fermentation using three media.Eighty-six natural compounds were isolated from four target strains,including nine new compounds.using modern chromatographic separation method and HPLC-DAD-UV series compound tracking separation method,and determined through modern spectroscopy technology and quantum chemical calculation method.Compounds 59 is the first indindoped alkaloids to be found with an amide group on C-3.Biological activity test show that compounds 33,41,50,61,70 and 74 had?-glycosidase inhibitory activity.Compounds 50 and 61 showed potent?-glucosidase inhibitory activity with IC₅₀values of 7.18 and 5.29?M,respectively,nearly 40 times that of the positive drug Acarbose.The docking simulation results demonstrated that compound 50 could interact with?-Glucosidase by forming one hydrogen bond and?-?interactions with residues PHE157.While compound 61 could generate one hydrogen bond with residues GLU 340 and also form?-?interactions with residues PHE 157 in?-Glucosidase.Compounds 32,33,70,74 and 75have anti-inflammatory activity inhibiting RAW264.7-induced nitrogen oxide synthase(i NOS)of mouse macrophages releasing massive nitrogen oxide(NO),The anti-inflammatory activity IC₅₀of compound 33 was 15.91?M,close to the positive control quercetin(IC₅₀was 14.18?M).At 100?M concentration,compounds 56 and 58,showed a clear activation effect against sf Ry R,which reduced the[Ca²⁺]_ERby 37.1 and 36.2%,respectively.Interestingly,both compounds showed no clear activation activity on r Ry R1.MTT assay was used to test the anti-tumor cytotoxic activity of some isolated compounds,which illustrated that compound Monocerin performed obvious inhibitory activity to human hepatoma cells(Huh-7).IC₅₀values were 13.92?g/m L(IC₅₀values for control cisplatin were 28.08?g/m L).Compound Monocerin had a stronger inhibitory effect on Huh-7 cells than that of cisplatin,which has the value for further research and development.Studies of the mechanism of action found that compound 14 could inhibit the migration and invasion of Huh-7 and block the cycle in the G1 phase,suggesting that compound 14 inhibits Huh-7 cell growth through control cycle regulation;The results of the small dish moth lethality experiment showed that compounds 69,70 and 74 all showed significant insecticide activity,with lethality above 70%and food rejection above 80%,which can be deeply studied as new insecticide lead compounds.This study further demonstrates that the special habitat fungal chemical components have novel structure and significant activity,enrich the natural product database,and provide potential active small molecule compounds for new drug development.