Introduction:Bioactive secondary metabolites from the microbes living in frigid,toxic or other extreme environments are emerging as a new medicinal resource.Here,we report the discovery of new antidiabetic and anti-in...Introduction:Bioactive secondary metabolites from the microbes living in frigid,toxic or other extreme environments are emerging as a new medicinal resource.Here,we report the discovery of new antidiabetic and anti-inflammatory compounds with novel structures from endophytic fungi hosted toxic medicinal plant.Methods:The endophytic fungus isolated from toxic plants was fermented and extracted.The obtained extracts were purified with preparative HPLC to yield pure compounds.The purified compounds were examined by PTP1b inhibition and NO inhibition assays to evaluate their bioactivities.Results:One new tridepsides(Compound 1),one new benzeneacetic acid derivative(Compound 3)and five known compounds(Compounds 2 and 4-7)were isolated from the ethyl acetate extract of Colletotrichum gloeosporioides,an endophytic fungus obtained from a toxic medicinal plant Tylophora ovata.Their structures were determined by spectroscopic data(1D and 2D NMR,HRESIMS)analyses.Compound 2 showed significant inhibitory activity against PTP1b with an IC50 value of 0.84μM.Compounds 2 and 3 exhibited moderate inhibitory activities against the NO(nitric oxide)release in LPS-induced RAW 264.7 cells at 10μM with percent inhibition of 39%and 33%,respectively.Conclusion:The Compound 2 has potent PTP1b inhibitory effect indicating its antidiabetic potential and thus might be considered a lead compound for antidiabetic drug development.展开更多
基金supported by grants from the National Natural Science Foundation of China[No.21732008]the Fundamental Research Funds for the Central Institutes(2018RC350007).
文摘Introduction:Bioactive secondary metabolites from the microbes living in frigid,toxic or other extreme environments are emerging as a new medicinal resource.Here,we report the discovery of new antidiabetic and anti-inflammatory compounds with novel structures from endophytic fungi hosted toxic medicinal plant.Methods:The endophytic fungus isolated from toxic plants was fermented and extracted.The obtained extracts were purified with preparative HPLC to yield pure compounds.The purified compounds were examined by PTP1b inhibition and NO inhibition assays to evaluate their bioactivities.Results:One new tridepsides(Compound 1),one new benzeneacetic acid derivative(Compound 3)and five known compounds(Compounds 2 and 4-7)were isolated from the ethyl acetate extract of Colletotrichum gloeosporioides,an endophytic fungus obtained from a toxic medicinal plant Tylophora ovata.Their structures were determined by spectroscopic data(1D and 2D NMR,HRESIMS)analyses.Compound 2 showed significant inhibitory activity against PTP1b with an IC50 value of 0.84μM.Compounds 2 and 3 exhibited moderate inhibitory activities against the NO(nitric oxide)release in LPS-induced RAW 264.7 cells at 10μM with percent inhibition of 39%and 33%,respectively.Conclusion:The Compound 2 has potent PTP1b inhibitory effect indicating its antidiabetic potential and thus might be considered a lead compound for antidiabetic drug development.
