Studies On The Metabolites From Two Endophytic Fungi And Four Medicinal Plants And Their Bioactivities

This paper consists of three chapters.Chapter 1 discussed the studies on the metabolites and activities of two endophytic fungi,Cladosporium sp.7951 and Stachybotrys chartarum.Chapter 2 described the metabolites and activities of four medicinal plants,Centranthera grandiflora Benth.,Uncaria macrophylla Wall.,Piper sarmentosum Roxb.,Agrimonia pilosa Ldb.,sequentially.In the last chapter,we reviewed the research progress of phenylspirodrimanes.In our study,the techniques of phytochemical separation,in combination with spectral analysis（NMR,HRMS,IR,UV,CD）,and quantum chemistry calculation methods（ECD）were applied to isolate and identify the chemical ingredients from the above plants.Overall,121 compounds were isolated and elucidated,among which 16were new ones,including the types of phenylspirodrimane,iridoids,alkaloids,flavones,triterpenes,and coumarins.Chapter 1.Metabolites from two endophytic fungi and their bioactivitiesEight new aspulvinone analogues,aspulvins A-H and 16 known compounds were isolated from cultures of the endophytic fungus Cladosporium sp.7951.All isolated aspulvinone analogues displayed different degrees of inhibitory activity against SARS-Co V-2 M^pro at 10μM.Notably,aspulvinones D,M,and R showed potential SARS-Co V-2 M^pro inhibition with IC₅₀ values of 10.3±0.6,9.4±0.6,and 7.7±0.6μM,respectively.Aspulvinone M showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage,IL-1βmaturation,NLRP3 inflammasome activation,and pyroptosis.The findings reveal that aspulvinones D,M,and R could be promising candidates for COVID-19 treatment as they inhibit SARS-Co V-2 infection and reduce inflammatory reactions caused by SARS-Co V-2.Five new phenylspirodrimanes,together with six known compounds,were isolated from cultures of the endophytic fungus Stachybotrys chartarum.It is worth mentioning that stachybotrydimer A is a rare phenylspirodrimane dimer,which is different from the reported common dimerization mode directly connected by C-C single bond,and its biogenic synthesis pathway is reasonably deduced.In the further activity study,stachybotrydimer A showed cell proliferation inhibitory activities on human cancer cells HCT-116 and SW620 with IC₅₀ values of 66.85±0.791μM and 46.18±0.321μM.Chapter 2.Chemical constituents from four medicinal plants and their bioactivitiesA new ionone glycoside,named centrantheroside F,together with 15 known compounds,were isolated from the roots of Centranthera grandiflora.The absolute configuration of centrantheroside F was confirmed via the analysis of 2D NMR and electronic circular dichroism（ECD）data.A pair of new oxindole alkaloids,named macrophyllines C and D,together with 19known compounds were isolated from Uncaria macrophylla.In addition,isorhynchophylline and corynoxine showed weak anti-HIV activities with EC₅₀ values of 18.77±1.28μM and 30.02±3.73μM,respectively.To investigate the chemical constituents of Piper sarmentosum,25 compounds were isolated and identified,including 16 alkaloids,4 sesquiterpenes,2 lignins,2aromatic hydrocarbons and 1 triterpene.The inhibitory activity of the isolates on LPS induced NO production was evaluated.Agrimonia pilosa has been used to treat enteritis in folk medicine for a long time.24compounds were isolated from Agrimonia pilosa,and their structures were determined by spectroscopic data analyses and comparing with the literature data.The antifungal activities of the isolates were tested.Chapter 3.Review of phenylspirodrimanesIn this chapter,we reviewed the progress of structures,biological activities of phenylspirodrimanes up to 2021.