An investigation of the mangrove-derived fungus Penicillium sp.DM27 led to the isolation of 19 new compounds,including three pairs of piperidinone enantiomers(±)-1,(±)-2,and(±)-3,two pairs of pyrrolidin...An investigation of the mangrove-derived fungus Penicillium sp.DM27 led to the isolation of 19 new compounds,including three pairs of piperidinone enantiomers(±)-1,(±)-2,and(±)-3,two pairs of pyrrolidinone enantiomers(±)-4 and(±)-5,and nine pyrrolidine derivatives 6−14.The structures of 1−14 were elucidated through NMR and HRESIMS analysis,coupled with experimental and calculated ECD spectroscopy and the modified Mosher method.Quantitative real time PCR and Western bolt analyses revealed that 11 blocked EMT in TGF-β1-treated HK-2 cells and suppressed fibroblast activation in TGF-β1-stimulated NIH-3T3 cells.Molecular simulations demonstrated that compound 11 could dock ADAM17,showing a high negative binding affinity.Additionally,the overexpression of ADAM17 by lentiviral infection triggered renal tubular EMT,while compound 11 suppressed this process.Overall,our research suggests that pyrrolidine derivatives may be potential therapeutic agents for the treatment of fibrotic kidney disease.展开更多
基金supported by the National Key Research and Development Program of China(No.2021YFC2100600),the National Natural Science Foundation of China(Nos.81973201,82200773,82370696,82204225,82200807),the Natural Science Foundation of Hubei Province(Nos.2021CFB347,2021CFB061),the Fundamental Research Funds for Central University(2042022kf1140),the Program of Excellent Doctoral(Postdoctoral)of Zhongnan Hospital of Wuhan University(ZNYB2021029),the Hubei Province Health and Family Planning Scientific Research Project(WJ2019MB103),the Clinical Research Project for Wu Jieping Medical Foundation(320.6750.19089-58),and the Research Fund from Medical Sci-Tech Innovation Platform of Zhongnan Hospital,Wuhan University(PTXM2020028,XKJS202035).We thank Dr.Ran Zhang from the Core Facility of Wuhan University and Dr.Xue Zhou from the Core Research Facilities of CCMS(WHU)for their assistance with NMR analysis.
文摘An investigation of the mangrove-derived fungus Penicillium sp.DM27 led to the isolation of 19 new compounds,including three pairs of piperidinone enantiomers(±)-1,(±)-2,and(±)-3,two pairs of pyrrolidinone enantiomers(±)-4 and(±)-5,and nine pyrrolidine derivatives 6−14.The structures of 1−14 were elucidated through NMR and HRESIMS analysis,coupled with experimental and calculated ECD spectroscopy and the modified Mosher method.Quantitative real time PCR and Western bolt analyses revealed that 11 blocked EMT in TGF-β1-treated HK-2 cells and suppressed fibroblast activation in TGF-β1-stimulated NIH-3T3 cells.Molecular simulations demonstrated that compound 11 could dock ADAM17,showing a high negative binding affinity.Additionally,the overexpression of ADAM17 by lentiviral infection triggered renal tubular EMT,while compound 11 suppressed this process.Overall,our research suggests that pyrrolidine derivatives may be potential therapeutic agents for the treatment of fibrotic kidney disease.
