Tumor necrosis factor-α(TNF-α)is a promising target for inflammatory and autoimmune diseases.Spirohypertones A(1)and B(2),two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skelet...Tumor necrosis factor-α(TNF-α)is a promising target for inflammatory and autoimmune diseases.Spirohypertones A(1)and B(2),two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons,were isolated from Hypericum patulum.The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis,single-crystal X-ray diffraction and electronic circular dichroism calculations.Importantly,2 showed remarkable TNF-αinhibitory activity,which could protect L929 cells from death induced by co-incubation with TNF-αand actinomycin D.It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-α.Notably,in an imiquimod-induced psoriasis murine model,2 restrained symptoms of epidermal hyperplasia associated with psoriasis,presenting anti-inflammatory and antiproliferative effects.This discovery positions 2 as a potent TNF-αinhibitor,providing a promising lead compound for developing an antipsoriatic agent.展开更多
Six new meroterpe no ids,bipolarinoids A-F(1-6),and two known congen ers(7-8)were isolated from a soil-derived fungus Bipolaris zeicola.Their structures were elucidated based on extensive spectroscopic techniques(inel...Six new meroterpe no ids,bipolarinoids A-F(1-6),and two known congen ers(7-8)were isolated from a soil-derived fungus Bipolaris zeicola.Their structures were elucidated based on extensive spectroscopic techniques(ineluding HRESIMS and ID and 2D NMR data),and the absolute configurations of 1-4 were further confirmed viasingle-crystal X-ray diffraction an alysis and comparis on of experimental electronic circular dichroism(ECD)data.Structurally,compound 1 represents the first case of cochlioquinone derivatives featuring a formaldehyde group at C-11, and compou nd 3 features a rareamino group at C-11.In the immunosuppressive activity assay,compounds 5-8 showed potent inhibitory activity against concanavalin A(ConA)-induced T lymphocyte proliferation with IC50 values of 78.3,81.1,48.3,and 48.0 nmol/L,respectively,which provided promising leads for designing and developing new im-muno suppressive agents to treat auto-immunological diseases.展开更多
Hybeanones A and B(1 and 2),two highly oxygenated and rearranged polycyclic polyprenylated acylphloroglucinols(PPAPs),were isolated from the aerial parts of Hypericum beanii.Their structures comprising absolute config...Hybeanones A and B(1 and 2),two highly oxygenated and rearranged polycyclic polyprenylated acylphloroglucinols(PPAPs),were isolated from the aerial parts of Hypericum beanii.Their structures comprising absolute configurations were elucidated by spectroscopic analysis,single-crystal X-ray diffraction,and quantum chemical calculations.Compounds 1 and 2 are defined by a newly assembled cyclopentanone unit fused to a tricyclic γ-lactone unit via a ketone carbonyl.The breakage of C-1/C-2 linkage via retro-Claisen reaction,attack from C-1 to C-19,and Baeyer-Villiger oxidation at C-1/C-23 bond were presumed to be the key steps in the assembly of 1 and 2.The isolates 1 and 2 showed potential acetylcholinesterase(AchE)inhibitory activities,with IC50 values of 21.34±1.48 and 18.79±2.36μmol/L,respectively.展开更多
Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this disease.In our continuous study of bioactive natural products from fungi,the first ergosterol-p...Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this disease.In our continuous study of bioactive natural products from fungi,the first ergosterol-polyether adducts,polyaspers A(1)and B(2),along with two known ergosterols,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol B(4),were iso-lated from Aspergillus sp.TJ507.Structure elucidation was accomplished by extensive spectroscopic analysis and single-crystal X-ray diffraction tests.Polyaspers A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system,and their biosynthetic path-ways were proposed to include intermolecular cyclization and Diels-Alder reactions.Activity screen of these isolates showed that 1-3 could improve the cell viability in an actinomycin D/TNF-αinduced L929 cells death model,with the EC50 values of 49.85,46.75 and 4.99μmol/L,respectively,and the activity of 3 was even comparable with that of the positive control SPD304.Further bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF-αin HaCaT cells.In an imiquimod-induced psoriasis murine model,3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL-17 and IL-23,presenting an anti-psoriatic effect.As such,those ergosterol derivatives,might serve as lead compounds for the development of novel TNF-αinhibitory agents in the clinical treatment of psoriasis.展开更多
基金supported by the Program for Changjiang Scholars of Ministry of Education of the People's Republic of China(T2016088)the National Natural Science Foundation for Distinguished Young Scholars(81725021,China)the National Natural Science Foundation of China(Nos.82003633,32100321 and 32300335)+4 种基金the National Natural Science Foundation of Hubei Province(2023AFB791 and 2023AFB530,China)Knowledge Innovation Project of Wuhan Science and Technology Bureau(2023020201020534,China)the Research and Development Program of Hubei Province(2020BCA058,China)the Open Foundation of Hubei Key Laboratory of Wudang Local Chinese Medicine Research(WDCM2023010,China)Funded by Open Research Fund Program of State Key Laboratory of Biocatalysis and Enzyme Engineering(SKLBEE2023003,China).
文摘Tumor necrosis factor-α(TNF-α)is a promising target for inflammatory and autoimmune diseases.Spirohypertones A(1)and B(2),two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons,were isolated from Hypericum patulum.The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis,single-crystal X-ray diffraction and electronic circular dichroism calculations.Importantly,2 showed remarkable TNF-αinhibitory activity,which could protect L929 cells from death induced by co-incubation with TNF-αand actinomycin D.It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-α.Notably,in an imiquimod-induced psoriasis murine model,2 restrained symptoms of epidermal hyperplasia associated with psoriasis,presenting anti-inflammatory and antiproliferative effects.This discovery positions 2 as a potent TNF-αinhibitor,providing a promising lead compound for developing an antipsoriatic agent.
基金supported by the National Natural Science Foundation of China(Nos.81573316 and 32000045)the National Science Fund for Distinguished Young Scholars(No.81725021)+2 种基金the Innovative Research Groups of the National Natural Science Foundation of China(No.81721005)the Tongji-Rongcheng Center for Biomedici ne,Huazhong University of Science and Technology(No.0231514141)the Research and Development Program of Hubei Provinee(No.2020BCA058).
文摘Six new meroterpe no ids,bipolarinoids A-F(1-6),and two known congen ers(7-8)were isolated from a soil-derived fungus Bipolaris zeicola.Their structures were elucidated based on extensive spectroscopic techniques(ineluding HRESIMS and ID and 2D NMR data),and the absolute configurations of 1-4 were further confirmed viasingle-crystal X-ray diffraction an alysis and comparis on of experimental electronic circular dichroism(ECD)data.Structurally,compound 1 represents the first case of cochlioquinone derivatives featuring a formaldehyde group at C-11, and compou nd 3 features a rareamino group at C-11.In the immunosuppressive activity assay,compounds 5-8 showed potent inhibitory activity against concanavalin A(ConA)-induced T lymphocyte proliferation with IC50 values of 78.3,81.1,48.3,and 48.0 nmol/L,respectively,which provided promising leads for designing and developing new im-muno suppressive agents to treat auto-immunological diseases.
基金financially supported by the National Natural Science Foundation for Distinguished Young Scholars(81725021)the National Science and Technology Project of China(2018ZX09201001-001-003)+4 种基金the Innovative Research Groups of the National Natural Science Foundation of China(81721005)the National Natural Science Foundation of China(82003633)the Academic Frontier Youth Team of HUST(2017QYTD19)the Fundamental Research Funds for the Central Universities(2020kfyXJJS083)the Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College(HUST).
文摘Hybeanones A and B(1 and 2),two highly oxygenated and rearranged polycyclic polyprenylated acylphloroglucinols(PPAPs),were isolated from the aerial parts of Hypericum beanii.Their structures comprising absolute configurations were elucidated by spectroscopic analysis,single-crystal X-ray diffraction,and quantum chemical calculations.Compounds 1 and 2 are defined by a newly assembled cyclopentanone unit fused to a tricyclic γ-lactone unit via a ketone carbonyl.The breakage of C-1/C-2 linkage via retro-Claisen reaction,attack from C-1 to C-19,and Baeyer-Villiger oxidation at C-1/C-23 bond were presumed to be the key steps in the assembly of 1 and 2.The isolates 1 and 2 showed potential acetylcholinesterase(AchE)inhibitory activities,with IC50 values of 21.34±1.48 and 18.79±2.36μmol/L,respectively.
基金supported financially by the National Natural Science Foundation for Distinguished Young Scholars (No.81725021)the National Natural Science Foundation of China (Nos.82003633,82173705 and 31972865)+2 种基金the Natural Science Foundation of Hubei Province (2023AFB791)the Research and Development Program of Hubei Province (2020BCA058)the Open Foundation of Hubei Key Laboratory of Wudang Local Chinese Medicine Research (WDCM2023010).
文摘Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this disease.In our continuous study of bioactive natural products from fungi,the first ergosterol-polyether adducts,polyaspers A(1)and B(2),along with two known ergosterols,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol B(4),were iso-lated from Aspergillus sp.TJ507.Structure elucidation was accomplished by extensive spectroscopic analysis and single-crystal X-ray diffraction tests.Polyaspers A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system,and their biosynthetic path-ways were proposed to include intermolecular cyclization and Diels-Alder reactions.Activity screen of these isolates showed that 1-3 could improve the cell viability in an actinomycin D/TNF-αinduced L929 cells death model,with the EC50 values of 49.85,46.75 and 4.99μmol/L,respectively,and the activity of 3 was even comparable with that of the positive control SPD304.Further bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF-αin HaCaT cells.In an imiquimod-induced psoriasis murine model,3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL-17 and IL-23,presenting an anti-psoriatic effect.As such,those ergosterol derivatives,might serve as lead compounds for the development of novel TNF-αinhibitory agents in the clinical treatment of psoriasis.