Hyparillums A(1)and B(2),two previously unidentified polycyclic polyprenylated acylphloroglucinols(PPAPs)with intricate architectures,were isolated from Hypericum patulum Thunb.Hyparillum A was the first PPAP with eig...Hyparillums A(1)and B(2),two previously unidentified polycyclic polyprenylated acylphloroglucinols(PPAPs)with intricate architectures,were isolated from Hypericum patulum Thunb.Hyparillum A was the first PPAP with eight-carbon rings based on an unprecedented 6/6/5/6/6/5/6/4 octocyclic system featuring a rare heptacyclo[10.8.1.11,10.03,8.08,21.012,19.014,17]docosane core.In contrast,hyparillum B featured a novel heptacyclic architecture(6/6/5/6/6/5/5)based on a hexacyclo[9.6.1.11,9.03,7.07,18.011,16]nonadecane motif.Furthermore,hyparillums A and B demonstrated promising inhibitory effects on the proliferation of murine splenocytes stimulated by anti-CD3/anti-CD28 monoclonal antibodies and lipopolysaccharide,exhibiting half-maximal inhibitory concentration(IC50)values ranging from 6.13±0.86 to 12.69±1.31μmol·L−1.展开更多
Hyperinoids A(1)and B(2),two prenylated acylphloroglucinol related meroterpenoids,were isolated from Hypericum patulum.Compound 1 incorporates an unprecedented 11,12-dioxatetracyclo[5.4.3.01,7.04,14]tetradecane system...Hyperinoids A(1)and B(2),two prenylated acylphloroglucinol related meroterpenoids,were isolated from Hypericum patulum.Compound 1 incorporates an unprecedented 11,12-dioxatetracyclo[5.4.3.01,7.04,14]tetradecane system,while 2 possesses a unique 10,11-dioxatetracyclo[5.3.3.01,7.04,13]tridecane syste m.Their structures were established by spectro scopic analysis and X-ray crystallographic data.Compounds 1 and 2 were identified as potent NF-κB inhibitors and suppressed the LPS-induced inflammatory responses in RAW 246.7 macrophages and primary mouse BMDM cells.展开更多
Spirohypatone A(1),a spirocyclic PPAP(polycyclic polyprenylated acylphloroglucinol) bearing an unprecedented hexahydro-1’H-spiro[cyclohexane-1,2’-pentalene]-2,4,6-trione core and a new homologue(spirohypatone B,2) w...Spirohypatone A(1),a spirocyclic PPAP(polycyclic polyprenylated acylphloroglucinol) bearing an unprecedented hexahydro-1’H-spiro[cyclohexane-1,2’-pentalene]-2,4,6-trione core and a new homologue(spirohypatone B,2) were isolated from Hypericum patulum together with two known biosynthetic precursors.Compound 1 represents the first spirocyclic PPAP possessing a 5/5/6 carbon ring system,biogenetically derived from the intermediate 3(attack from C-3 to C-12),which was differed from normal spirocyclic PPAPs(attack from C-3 to C-11).In addition,through extensive spectroscopic analysis,an interconversion mechanism of keto-enol of 1 was postulated and confirmed by its methylated reaction.The structures and absolute configurations of 1 and 2 were determined by comprehensive spectroscopic and chemical derivatized methods and X-ray crystallography.Compounds 1,2,and 4 were tested to exhibit cytotoxic activities against several cancer cell lines.展开更多
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
基金supported by the Program for Changjiang Scholars of Ministry of Education of the People’s Republic of China(No.T2016088)the National Natural Science Foundation for Distinguished Young Scholars(No.81725021)+5 种基金the National Science and Technology Project of China(No.2018ZX09201001-001-003)the National Natural Science Foundation of China(Nos.82003633,32100321,and 32300335)the Research and Development Program of Hubei Province(No.2020BCA058)the Open Foundation of Hubei Key Laboratory of Wudang Local Chinese Medicine Research(No.WDCM2022003)the National Natural Science Foundation of Hubei Province(No.2023AFB530)the Knowledge Innovation Project of Wuhan Science and Technology Bureau(No.2023020201020534).
文摘Hyparillums A(1)and B(2),two previously unidentified polycyclic polyprenylated acylphloroglucinols(PPAPs)with intricate architectures,were isolated from Hypericum patulum Thunb.Hyparillum A was the first PPAP with eight-carbon rings based on an unprecedented 6/6/5/6/6/5/6/4 octocyclic system featuring a rare heptacyclo[10.8.1.11,10.03,8.08,21.012,19.014,17]docosane core.In contrast,hyparillum B featured a novel heptacyclic architecture(6/6/5/6/6/5/5)based on a hexacyclo[9.6.1.11,9.03,7.07,18.011,16]nonadecane motif.Furthermore,hyparillums A and B demonstrated promising inhibitory effects on the proliferation of murine splenocytes stimulated by anti-CD3/anti-CD28 monoclonal antibodies and lipopolysaccharide,exhibiting half-maximal inhibitory concentration(IC50)values ranging from 6.13±0.86 to 12.69±1.31μmol·L−1.
基金financially supported by Fudan-SIMM Joint Research Fund(No.FU-SIMM20181011)。
文摘Hyperinoids A(1)and B(2),two prenylated acylphloroglucinol related meroterpenoids,were isolated from Hypericum patulum.Compound 1 incorporates an unprecedented 11,12-dioxatetracyclo[5.4.3.01,7.04,14]tetradecane system,while 2 possesses a unique 10,11-dioxatetracyclo[5.3.3.01,7.04,13]tridecane syste m.Their structures were established by spectro scopic analysis and X-ray crystallographic data.Compounds 1 and 2 were identified as potent NF-κB inhibitors and suppressed the LPS-induced inflammatory responses in RAW 246.7 macrophages and primary mouse BMDM cells.
基金financially supported by the NSFC-Joint Foundation of Yunnan Province(No.U1902213)the Second Tibetan Plateau Scientific Expedition and Research(STEP)Program(No.2019QZKK0502020303)+1 种基金Southeast Asia Biodiversity Research Institute,CAS(No.2017CASSEABRIQG003)the Natural Sciences Foundation of Yunnan Province(No.2019FA003)。
文摘Spirohypatone A(1),a spirocyclic PPAP(polycyclic polyprenylated acylphloroglucinol) bearing an unprecedented hexahydro-1’H-spiro[cyclohexane-1,2’-pentalene]-2,4,6-trione core and a new homologue(spirohypatone B,2) were isolated from Hypericum patulum together with two known biosynthetic precursors.Compound 1 represents the first spirocyclic PPAP possessing a 5/5/6 carbon ring system,biogenetically derived from the intermediate 3(attack from C-3 to C-12),which was differed from normal spirocyclic PPAPs(attack from C-3 to C-11).In addition,through extensive spectroscopic analysis,an interconversion mechanism of keto-enol of 1 was postulated and confirmed by its methylated reaction.The structures and absolute configurations of 1 and 2 were determined by comprehensive spectroscopic and chemical derivatized methods and X-ray crystallography.Compounds 1,2,and 4 were tested to exhibit cytotoxic activities against several cancer cell lines.
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.
