Chronic superficial gastritis(CSG)is a common disease of the digestive system that possesses a serious pathogenesis.Jinhong tablet(JHT),a traditional Chinese medicine(TCM)prescription,exerts therapeutic effects agains...Chronic superficial gastritis(CSG)is a common disease of the digestive system that possesses a serious pathogenesis.Jinhong tablet(JHT),a traditional Chinese medicine(TCM)prescription,exerts therapeutic effects against CSG.However,the molecular basis of its therapeutic effect has not been clarified.Herein,we employed ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q/TOF-MS)based chemical profile identification to determine the chemical components in JHT.Further,we applied network pharmacology to illustrate its molecular mechanisms.A total of 96 chemical constituents were identified in JHT,31 of which were confirmed using reference standards.Based on the bioinformatics analysis using the symptom-guided pharmacological networks of“chi,”“blood,”“pain,”and“inflammation,”and target screening through the interaction probabilities between compounds and targets,matrix metalloproteinase 2(MMP2),dopamine d2 receptor(DRD2),and Aldo-keto reductase family 1 member B1(AKR1B1)were identified as key targets in the therapeutic effect exhibited by JHT against CSG.Moreover,according to the inhibitory activities presented in the literature and binding mode analysis,the structural types of alkaloids,flavonoids,organic acids,including chlorogenic acid(10),caffeic acid(13),(-)-corydalmine(33),(-)-isocorypalmine(36),isochlorogenic acid C(38),isochlorogenic acid A(41),quercetin-3-O-a-L-rhamnoside(42),isochlorogenic acid B(47),quercetin(63),and kaempferol(70)tended to show remarkable activities against CSG.Owing to the above findings,we systematically identified the chemical components of JHT and revealed its molecular mechanisms based on the symptoms associated with CSG.展开更多
A new electrochemical sensor for organophosphate pesticide(methyl-paraoxon)detection based on bifunctional cerium oxide(CeO_(2))nanozyme is here reported for the first time.Methyl-paraoxon was degraded into p-nitrophe...A new electrochemical sensor for organophosphate pesticide(methyl-paraoxon)detection based on bifunctional cerium oxide(CeO_(2))nanozyme is here reported for the first time.Methyl-paraoxon was degraded into p-nitrophenol by using CeO_(2) with phosphatase mimicking activity.The CeO_(2) nanozymemodified electrode was then synthesized to detect p-nitrophenol.Cyclic voltammetry was applied to investigate the electrochemical behavior of the modified electrode,which indicates that the signal enhancement effect may attribute to the coating of CeO_(2) nanozyme.The current research also studied and discussed the main parameters affecting the analytical signal,including accumulation potential,accumulation time,and pH.Under the optimum conditions,the present method provided a wider linear range from 0.1 to 100 mmol/L for methyl-paraoxon with a detection limit of 0.06 mmol/L.To validate the proof of concept,the electrochemical sensor was then successfully applied for the determination of methyl-paraoxon in three herb samples,i.e.,Coix lacryma-jobi,Adenophora stricta and Semen nelumbinis.Our findings may provide new insights into the application of bifunctional nanozyme in electrochemical detection of organophosphorus pesticide.展开更多
Myrcauones A-D(1-4),four new phloroglucinol-terpene adducts were isolated from the leaves of Myrciaria cauliflora.Their structures with absolute configurations were elucidated by combination of spectroscopic analysis,...Myrcauones A-D(1-4),four new phloroglucinol-terpene adducts were isolated from the leaves of Myrciaria cauliflora.Their structures with absolute configurations were elucidated by combination of spectroscopic analysis,single crystal X-ray diffraction,and electronic circular dichroism(ECD)calculations.Compound 1 was a rearranged isobutylphloroglucinol-pinene adduct featuring an unusual 2,3,4,4a,10,11-hexahydro-1H-3,11a-methanodibenzo[b,f]oxepin backbone.Compound 4 showed moderate antibacterial activity against Gram-positive bacteria including multiresistant strains.展开更多
Microbial transformation is a useful tool for structure modification of active natural products.Z-Butylidenephthalide is the main active constituent of Angelica sinensis.In the present work,a pair of new oxidized meta...Microbial transformation is a useful tool for structure modification of active natural products.Z-Butylidenephthalide is the main active constituent of Angelica sinensis.In the present work,a pair of new oxidized metabolites,namely(-)(11R)-(Z)-11-hydroxy-butylidenephthalide(1a)and(+)(11S)-(Z)-11-hydroxy-butylidenephthalide(1b),were obtained from microbial transformation for region-selective 11-hydroxylation of Z-butylidenephthalide by Aspergillus niger CGMCC 3.739.Their structures,including absolute configurations,were elucidated by extensive analysis of HR-ESI-MS,NMR spectra,and the modified Mosher’s method.This is the first study on the microbial transformation of Z-butylidenephthalide,and these findings offer a tool for region-selective 11-hydroxylation of Z-butylidenephthalide.展开更多
Fivenovel Daphniphyllum alkaloids,named dcalycinumines A-E(1-4,6),andeight previously described Daphniphyllum alkaloids(5,7-13)were isolated from Daphniphyllum calycinum.Compound 1 is the first Daphniphyllum alkaloid ...Fivenovel Daphniphyllum alkaloids,named dcalycinumines A-E(1-4,6),andeight previously described Daphniphyllum alkaloids(5,7-13)were isolated from Daphniphyllum calycinum.Compound 1 is the first Daphniphyllum alkaloid possessing a highly rearranged 6/6/6/7/5/6 hexacyclic architecture with a unique 3-methyl-1-azabicyclo[4,4,0]decane ring system.Compound 2 represents a rare diamino Daphniphyllum alkaloid with an unprecedented 6/5/5/6/6/5 carbon skeleton featuring a unique 1-aza-6-azaspiro[4,5]decane unit,whereas 3 also represents a rare diamino Daphniphyllum alkaloid as a possible precursor of 2.Compound 4 is the second example of c-22-nor yuzurimine-type alkaloids.Their structures and absolute configurations were elucidated by HRESIMS,NMR spectroscopic analyses,EcD calculations,and single-crystal X-ray diffraction.Moreover,compound 1 showed remarkable antitumor activities,which could inhibit the proliferation,migration and invasion of nasopharyngeal carcinoma cells,and promoted nasopharyngeal carcinoma cells apoptosis.展开更多
Fusagerins A–F(1–6),six new alkaloids including a unique one with the rare a-(N-formyl)carboxamide moiety(1),a hydantoin(imidazolidin-2,4-dione)derivative(2),and four fungerin analogues(3–6),were isolated from the ...Fusagerins A–F(1–6),six new alkaloids including a unique one with the rare a-(N-formyl)carboxamide moiety(1),a hydantoin(imidazolidin-2,4-dione)derivative(2),and four fungerin analogues(3–6),were isolated from the crude extract of the fungus Fusarium sp.,together with the known compound fungerin(7).Compound 2 was isolated as a racemate and further separated into two enantiomers on a chiral HPLC column.The structures of 1–6 were determined mainly by NMR experiments,and the absolute configuration of 1 and 2 was assigned by electronic circular dichroism(ECD)calculations.Compound 7 showed antibacterial activity against Staphylococcus aureus and Streptococcus pneumoniae,and weak cytotoxicity against the T24 cells.展开更多
Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by exte...Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism(ECD)calculation.Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.展开更多
A pair of new tirucallane triterpenoid epimers,picraquassins M and N(1 and 2),were isolated from the stems of Picrasma quassioides(D.Don)Benn.Their structures were determined based on comprehensive spectroscopic and X...A pair of new tirucallane triterpenoid epimers,picraquassins M and N(1 and 2),were isolated from the stems of Picrasma quassioides(D.Don)Benn.Their structures were determined based on comprehensive spectroscopic and X-ray crystallographic analyses.In addition,their ACh E inhibitory activity,cytotoxicity against five human tumour cell lines(SW480,MCF-7,HepG2,Hela,and PANC-1),and antimicrobial activity against two bacteria(Staphylococcus.aureus 209 P and Escherichia coli ATCC0111)and two fungi(Candida albicans FIM709 and Aspergillus niger R330)were evaluated.展开更多
Sodium taurocholate cotransporting polypeptide(NTCP)is identified as the functional receptor for HBV entry,which is responsible for upregulated HBV transcription in the HBV life cycle.Besides,NTCP is also implicated i...Sodium taurocholate cotransporting polypeptide(NTCP)is identified as the functional receptor for HBV entry,which is responsible for upregulated HBV transcription in the HBV life cycle.Besides,NTCP is also implicated in the progression of HBV-induced hepatocellular carcinoma(HCC).Thereby,NTCP-targeting entry inhibitors are proposed to suppress HBV infection and replication in HBV-induced hepatoma therapy.Herein,we integrated in silico screening and chemical synthesis to obtain a small-molecule NTCP inhibitor B7,which exhibited moderate anti-proliferative activities against HepG2 cells and anti-HBV activity in vitro.Additionally,CETSA assay,molecular docking,and MD simulation validated that B7 could bind to NTCP.Furthermore,western blot analysis demonstrated that B7 induced apoptosis with an increased expression of Bax and caspase 3 cleaving as well as a decreasing expression of Bcl-2 in HepG2 cells.Taken together,our study identified B7 as a novel NTCP inhibitor with anti-proliferation activities which might provide a new opportunity for HCC therapy.展开更多
Five new sesquiterpenoids(1-5),chloranholides A-E,along with three known compounds(6-8),were isolated from the whole plants of Chloranthus holostegius.Their structures were elucidated using the spectroscopic methods(I...Five new sesquiterpenoids(1-5),chloranholides A-E,along with three known compounds(6-8),were isolated from the whole plants of Chloranthus holostegius.Their structures were elucidated using the spectroscopic methods(IR,UV,HR-ESI-MS,ID and 2D NMR),and their absolute configurations were determined by the X-ray crystallography and ECD calculation.Compounds 1-8 were evaluated for their anti-inflammatory effects on LPS-induced RAW 264.7 macrophage cells.Especially,compound 4 exhibited the most significant anti-inflammatory activity with the secretion levels of TNF-α and IL-6 at 15.52%and 5.98%,respectively,better than that of dexamethasone.展开更多
Biotransformation ofα-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans,(+)(7 S,8 S,7’S,8’R)iso-magnosalicin(1 a)/(-)(7 R,8 R,7’R,8’S)iso-magnosalicin(1 b)and(+)(7 R,8 R,7’S,8’R)ma...Biotransformation ofα-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans,(+)(7 S,8 S,7’S,8’R)iso-magnosalicin(1 a)/(-)(7 R,8 R,7’R,8’S)iso-magnosalicin(1 b)and(+)(7 R,8 R,7’S,8’R)magnosalicin(2 a)/(-)(7 S,8 S,7’R,8’S)magnosalicin(2 b),and four known metabolites,(±)acoraminol A(3),(±)acoraminol B(4),asaraldehyde(5),and 2,4,5-trimethoxybenzoic acid(6).Their structures,including absolute configurations,were determined by extensive analysis of NMR spectra,X-ray crystallography,and quantum chemical ECD calculations.The cytotoxic activity and Aβ_(42)aggregation inhibitory activity of all the compounds were evaluated.Compound 2 displayed significant anti-Aβ_(42)aggregation activity with an inhibitory rate of 60.81%(the positive control EGCG:69.17%).In addition the biotransformation pathway ofα-asarone by Alternaria longipes CGMCC 3.2875 was proposed.展开更多
Three new indole alkaloids, flueindolines A–C(1–3), along with nine known alkaloids(4–12), were isolated from the fruits of Flueggea virosa(Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indo...Three new indole alkaloids, flueindolines A–C(1–3), along with nine known alkaloids(4–12), were isolated from the fruits of Flueggea virosa(Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indole alkaloids possessing an unusual pyrido[1, 2-a]indole framework, and 3 presents a rare spiro(pyrrolizidinyl-oxindole) backbone. Their structures with absolute configurations were elucidated by means of comprehensive spectroscopic analysis, chemical calculation, as well as X-ray crystallography. Chiral resolution and absolute configuration determination of the known compounds 4, 10, and 11 were reported for the first time. The hypothetical biogenetical pathways of 1–3 were herein also proposed.展开更多
Triterpenes are derived from squalene or oxidosqualene.However,a new class of triterpenes derived from hexaprenyl pyrophosphate has been recently discovered,formed by a new family of chimeric class I triterpene syntha...Triterpenes are derived from squalene or oxidosqualene.However,a new class of triterpenes derived from hexaprenyl pyrophosphate has been recently discovered,formed by a new family of chimeric class I triterpene synthases.The cyclization mechanisms of triterpenes were elucidated by isotopic labeling and protein structural analyses,which helps understand the biosynthesis of triterpenes in nature.展开更多
From the fungus Trichoderma sp., we isolated seven novel 18-residue peptaibols, neoatroviridins E-K ( 1−7 ), and six new 14-residue peptaibols, harzianins NPDG J-O ( 8−13 ). Additionally, four previously characterized...From the fungus Trichoderma sp., we isolated seven novel 18-residue peptaibols, neoatroviridins E-K ( 1−7 ), and six new 14-residue peptaibols, harzianins NPDG J-O ( 8−13 ). Additionally, four previously characterized 18-residue peptaibols neoatroviridins A-D ( 14−17 ) were also identified. The structural configurations of the newly identified peptaibols ( 1−13 ) were determined by comprehensive nuclear magnetic resonance (NMR) and high-resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS/MS) data. Their absolute configurations were further determined using Marfey’s method. Notably, compounds 12 and 13 represent the first 14-residue peptaibols containing an acidic amino acid residue. In antimicrobial assessments, all 18-residue peptaibols ( 1 − 7 , 14 − 17 ) exhibited moderate inhibitory activities against Staphylococcus aureus 209P, with minimum inhibitory concentration (MIC) values ranging from 8−32 μg·mL^(−1). Moreover, compound 9 exhibited moderate inhibitory effect on Candida albicans FIM709, with a MIC value of 16 μg·mL^(−1).展开更多
The flower buds of Lonicera macranthoides(Shan Yin-Hua), represent an important traditional Chinese medicine and food ingredient. A phytochemical investigation of the 70% EtOH extract of the flower buds of L. macranth...The flower buds of Lonicera macranthoides(Shan Yin-Hua), represent an important traditional Chinese medicine and food ingredient. A phytochemical investigation of the 70% EtOH extract of the flower buds of L. macranthoides resulted in the isolation of 12 triterpenoids(1-12), including two new ursane-type nortriterpenes, 2α, 24-dihydroxy-23-nor-ursolic acid(1) and 2α, 4α-dihydroxy-23-nor-ursolic acid(2). Their structures were established by multiple spectroscopic methods and comparison with literature data. All isolated compounds were evaluated for their anti-inflammatory effects in LPS-activated RAW264.7 cells. Compounds 1 and 2 exhibited inhibitory effects on iNOS at the concentration of 30 μmol·L^(-1).展开更多
Sophaloseedlines A-G(1-7),seven new matrine-based alkaloids along with two known analogues,were isolated from the seeds of Sophora alopecuroides.The new structures were determined based on extensive spectroscopic data...Sophaloseedlines A-G(1-7),seven new matrine-based alkaloids along with two known analogues,were isolated from the seeds of Sophora alopecuroides.The new structures were determined based on extensive spectroscopic data,electronic circular dichroism calculations,and X-ray crystallography.Notably,sophaloseedline A(1)represents a novel rearranged 6(5→17)-abeo-matrine alkaloid featuring unprecedented highly constructed 7/6/5/6 tetracyclic fused ring skeleton.The hypothetical biosynthetic pathways for sophaloseedli nes A-F were proposed based on co-existing precursors.Additionally,all the isolated alkaloids were screened for their antiviral activities against hepatitis B virus,and new alkaloids 1 and 2 displayed more potent activities than those of matrine(a parent alkaloid of title plant)and positive control(lamivudine).展开更多
A phytochemical investigation on the seeds of Sophora alopecuroides led to obtaining fourteen structurally diverse matrine-based alkaloids(1-14),including eight new ones(1,6,8-12,14).Notably,alopecuroide F(1)represent...A phytochemical investigation on the seeds of Sophora alopecuroides led to obtaining fourteen structurally diverse matrine-based alkaloids(1-14),including eight new ones(1,6,8-12,14).Notably,alopecuroide F(1)represents the first dimeric matrine-type skeleton assembled via unprecedent C-13-C-12'connection.The new structures were determined through extensive spectroscopic data(UV,OR,HRESIMS,1D,and 2D NMR),ECD calculations,and three instances,verified by X-ray crystallography.Biologically,all alkaloids were evaluated for cytotoxicity against four human cancer cell lines(HepG2,A549,THP-1,and MCF-7)and anti-inflammatory activities for two pro-inflammatory cytokines(TNF-αand IL-6).Alopecuroide F(1)can inhibit TNF-αand IL-6 productions in a dose-dependent manner with IC50 values of 35.6±0.5 and 41.7±0.8μmol/L,respectively.展开更多
AIM:To investigate the chemical constituents of Vitex negundo.METHOD:Compounds were isolated by different chromatographic methods and their structures were elucidated on the basis of NMR spectroscopy.RESULTS:Four comp...AIM:To investigate the chemical constituents of Vitex negundo.METHOD:Compounds were isolated by different chromatographic methods and their structures were elucidated on the basis of NMR spectroscopy.RESULTS:Four compounds were isolated and identified as 2α,3α,24-trihydroxyurs-12,20(30)-dien-28-oic acid-28-O-β-D-glucopyranosyl ester(1),corosolic acid(2),vulgarsaponin A(3) and 2α,3α,24-trihydroxyurs-12-en-28-oic acid-28-O-β-Dglucopyranosyl ester(4),respectively.CONCLUSION:Compound 1 is a new triterpenoid glycoside.展开更多
A chemical investigation on Sporormiella sp.led to the isolation and structural elucidation of tripodalsporormielones Ae C(1-3),a new class of polyketide possessing unprecedented cage-like skeletons with polyvdent bri...A chemical investigation on Sporormiella sp.led to the isolation and structural elucidation of tripodalsporormielones Ae C(1-3),a new class of polyketide possessing unprecedented cage-like skeletons with polyvdent bridged and fused ring systems.These polyketides with cage-like skeletons were characterized as a high non-protonated carbon-containing system,which resulted in few HMBC correlations observed and made the accurate structures hard to be obtained by NMR.Especially,some signals of non-protonated sp;carbons are weak and even unobservable in compound 1.In order to establish the structure of 1,the calculated NMR with DP4 evaluation was applied to determine the structure from the plausible structure candidates obtained from the detailed NMR analysis.Based on NMR experiments and calculated NMR,the structures of isolated compounds were established and confirmed by X-ray technology.Through chiral isolation,the optically pure enantiomers of 1 and 3 were obtained,and their absolute configurations were determined based on ECD quantum chemical calculation.Based on the isolated compounds and our previous work,1-3 would be derived from 3-methylorcinaldehyde,and their plausible biosynthetic mechanism was proposed.Furthermore,1 exhibited obvious short-term memory improvement activity on an Alzheimer’s disease fly model.展开更多
基金funded by the National Natural Science Foundation of China (Grant Nos.: 81903426 and 81803347)
文摘Chronic superficial gastritis(CSG)is a common disease of the digestive system that possesses a serious pathogenesis.Jinhong tablet(JHT),a traditional Chinese medicine(TCM)prescription,exerts therapeutic effects against CSG.However,the molecular basis of its therapeutic effect has not been clarified.Herein,we employed ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q/TOF-MS)based chemical profile identification to determine the chemical components in JHT.Further,we applied network pharmacology to illustrate its molecular mechanisms.A total of 96 chemical constituents were identified in JHT,31 of which were confirmed using reference standards.Based on the bioinformatics analysis using the symptom-guided pharmacological networks of“chi,”“blood,”“pain,”and“inflammation,”and target screening through the interaction probabilities between compounds and targets,matrix metalloproteinase 2(MMP2),dopamine d2 receptor(DRD2),and Aldo-keto reductase family 1 member B1(AKR1B1)were identified as key targets in the therapeutic effect exhibited by JHT against CSG.Moreover,according to the inhibitory activities presented in the literature and binding mode analysis,the structural types of alkaloids,flavonoids,organic acids,including chlorogenic acid(10),caffeic acid(13),(-)-corydalmine(33),(-)-isocorypalmine(36),isochlorogenic acid C(38),isochlorogenic acid A(41),quercetin-3-O-a-L-rhamnoside(42),isochlorogenic acid B(47),quercetin(63),and kaempferol(70)tended to show remarkable activities against CSG.Owing to the above findings,we systematically identified the chemical components of JHT and revealed its molecular mechanisms based on the symptoms associated with CSG.
基金This work was supported by Macao Science and Technology Development Fund(Grant No.:0147/2019/A3)Guangxi Innovation-driven Development Special Foundation Project(Project No.:GuiKe AA18118049)+1 种基金China Postdoctoral Science Foundation(Grant No.:2019M653299)the National Natural Science Foundation of China(Grant No.:81903794).
文摘A new electrochemical sensor for organophosphate pesticide(methyl-paraoxon)detection based on bifunctional cerium oxide(CeO_(2))nanozyme is here reported for the first time.Methyl-paraoxon was degraded into p-nitrophenol by using CeO_(2) with phosphatase mimicking activity.The CeO_(2) nanozymemodified electrode was then synthesized to detect p-nitrophenol.Cyclic voltammetry was applied to investigate the electrochemical behavior of the modified electrode,which indicates that the signal enhancement effect may attribute to the coating of CeO_(2) nanozyme.The current research also studied and discussed the main parameters affecting the analytical signal,including accumulation potential,accumulation time,and pH.Under the optimum conditions,the present method provided a wider linear range from 0.1 to 100 mmol/L for methyl-paraoxon with a detection limit of 0.06 mmol/L.To validate the proof of concept,the electrochemical sensor was then successfully applied for the determination of methyl-paraoxon in three herb samples,i.e.,Coix lacryma-jobi,Adenophora stricta and Semen nelumbinis.Our findings may provide new insights into the application of bifunctional nanozyme in electrochemical detection of organophosphorus pesticide.
基金supported by the National Key R&D Program of China(No.2017YFC1703800)the Program for the National Natural Science Foundation of China(Nos.81822042,81630095)+2 种基金the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y036)Key-Area Research and Development Program of Guangdong Province(2020B1111110004)the High-performance Computing Platform of Jinan University.
文摘Myrcauones A-D(1-4),four new phloroglucinol-terpene adducts were isolated from the leaves of Myrciaria cauliflora.Their structures with absolute configurations were elucidated by combination of spectroscopic analysis,single crystal X-ray diffraction,and electronic circular dichroism(ECD)calculations.Compound 1 was a rearranged isobutylphloroglucinol-pinene adduct featuring an unusual 2,3,4,4a,10,11-hexahydro-1H-3,11a-methanodibenzo[b,f]oxepin backbone.Compound 4 showed moderate antibacterial activity against Gram-positive bacteria including multiresistant strains.
基金This work was financially supported by grants from the National Key Research and Development Program of China(2018 YFA0903200/2018YFA0903201)the National Natural Science Foundation of China(81925037/31900284)+3 种基金Chang Jiang Scholars Program(Young Scholar)from the Ministry of Education of China(Hao Gao,2017)National High-level Personnel of Special Support Program(2017RA2259)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y036)K.C.Wong Education Foundation(Hao Gao,2016).
文摘Microbial transformation is a useful tool for structure modification of active natural products.Z-Butylidenephthalide is the main active constituent of Angelica sinensis.In the present work,a pair of new oxidized metabolites,namely(-)(11R)-(Z)-11-hydroxy-butylidenephthalide(1a)and(+)(11S)-(Z)-11-hydroxy-butylidenephthalide(1b),were obtained from microbial transformation for region-selective 11-hydroxylation of Z-butylidenephthalide by Aspergillus niger CGMCC 3.739.Their structures,including absolute configurations,were elucidated by extensive analysis of HR-ESI-MS,NMR spectra,and the modified Mosher’s method.This is the first study on the microbial transformation of Z-butylidenephthalide,and these findings offer a tool for region-selective 11-hydroxylation of Z-butylidenephthalide.
基金supported by grants from the National Natural Science Foundation of China(Nos.82173695,82273803,82003743,81973190)the Guangdong Basic and Applied Basic Research Foundation(No.2020B1515020033)Scienceand Technology Planning Projectof Guangzhou City(No.202201010485).
文摘Fivenovel Daphniphyllum alkaloids,named dcalycinumines A-E(1-4,6),andeight previously described Daphniphyllum alkaloids(5,7-13)were isolated from Daphniphyllum calycinum.Compound 1 is the first Daphniphyllum alkaloid possessing a highly rearranged 6/6/6/7/5/6 hexacyclic architecture with a unique 3-methyl-1-azabicyclo[4,4,0]decane ring system.Compound 2 represents a rare diamino Daphniphyllum alkaloid with an unprecedented 6/5/5/6/6/5 carbon skeleton featuring a unique 1-aza-6-azaspiro[4,5]decane unit,whereas 3 also represents a rare diamino Daphniphyllum alkaloid as a possible precursor of 2.Compound 4 is the second example of c-22-nor yuzurimine-type alkaloids.Their structures and absolute configurations were elucidated by HRESIMS,NMR spectroscopic analyses,EcD calculations,and single-crystal X-ray diffraction.Moreover,compound 1 showed remarkable antitumor activities,which could inhibit the proliferation,migration and invasion of nasopharyngeal carcinoma cells,and promoted nasopharyngeal carcinoma cells apoptosis.
基金the National Natural Science Foundation of China(81273395)the National Program of Drug Research and Development(2012ZX09301-003).
文摘Fusagerins A–F(1–6),six new alkaloids including a unique one with the rare a-(N-formyl)carboxamide moiety(1),a hydantoin(imidazolidin-2,4-dione)derivative(2),and four fungerin analogues(3–6),were isolated from the crude extract of the fungus Fusarium sp.,together with the known compound fungerin(7).Compound 2 was isolated as a racemate and further separated into two enantiomers on a chiral HPLC column.The structures of 1–6 were determined mainly by NMR experiments,and the absolute configuration of 1 and 2 was assigned by electronic circular dichroism(ECD)calculations.Compound 7 showed antibacterial activity against Staphylococcus aureus and Streptococcus pneumoniae,and weak cytotoxicity against the T24 cells.
基金supported by the National Key R&D Program of China(No.2017YFC1703802)the National Natural Science Foundation of China(Nos.U1801287,81630095,and 81803398)+1 种基金the Science and Technology Planning Project of Guangdong Province(No.2018B020207008)the High-performance Super Computing Platform of Jinan University
文摘Four new corynanthe-type alkaloids,meloslines C–F(1–4),together with four known ones(5–8)were isolated from the roots of Alstonia scholaris.Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism(ECD)calculation.Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.
基金supported by grants from the National Key Research and Development Program of China(Nos.2018YFA0903200 and 2018YFA0903201)the National Natural Science Foundation of China(No.31761143016)+6 种基金Chang Jiang Scholars Program(GAO Hao,2017)from the Ministry of Education of ChinaNational High-level Personnel of Special Support Program(No.2017RA2259)Guangdong Special Support Program(No.2016TX03R280)Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(No.QNRC2-B06)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(GAO Hao,2014)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)K.C.Wong Education Foundation(GAO Hao,2016)
文摘A pair of new tirucallane triterpenoid epimers,picraquassins M and N(1 and 2),were isolated from the stems of Picrasma quassioides(D.Don)Benn.Their structures were determined based on comprehensive spectroscopic and X-ray crystallographic analyses.In addition,their ACh E inhibitory activity,cytotoxicity against five human tumour cell lines(SW480,MCF-7,HepG2,Hela,and PANC-1),and antimicrobial activity against two bacteria(Staphylococcus.aureus 209 P and Escherichia coli ATCC0111)and two fungi(Candida albicans FIM709 and Aspergillus niger R330)were evaluated.
基金supported by National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2018ZX09735005)the National Natural Science Foundation of China(Nos.81922064,81874290,81673290,81803347 and 81903502)+1 种基金the Natural Science Foundation of Guangdong Province(No.2018A030313707)Post-Doctor Research Project,West China Hospital,Sichuan University(No.2019HXBH034)。
文摘Sodium taurocholate cotransporting polypeptide(NTCP)is identified as the functional receptor for HBV entry,which is responsible for upregulated HBV transcription in the HBV life cycle.Besides,NTCP is also implicated in the progression of HBV-induced hepatocellular carcinoma(HCC).Thereby,NTCP-targeting entry inhibitors are proposed to suppress HBV infection and replication in HBV-induced hepatoma therapy.Herein,we integrated in silico screening and chemical synthesis to obtain a small-molecule NTCP inhibitor B7,which exhibited moderate anti-proliferative activities against HepG2 cells and anti-HBV activity in vitro.Additionally,CETSA assay,molecular docking,and MD simulation validated that B7 could bind to NTCP.Furthermore,western blot analysis demonstrated that B7 induced apoptosis with an increased expression of Bax and caspase 3 cleaving as well as a decreasing expression of Bcl-2 in HepG2 cells.Taken together,our study identified B7 as a novel NTCP inhibitor with anti-proliferation activities which might provide a new opportunity for HCC therapy.
基金the National Key R&D Program of China(No.2017YFC1703800)the National Natural Science Foundation of China(Nos.81973190,81803376)+3 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2020B1515020033)the Natural Science Foundation of Guangdong Province(No.2018B030311020)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)the high performance public computing service platform of Jinan University.
文摘Five new sesquiterpenoids(1-5),chloranholides A-E,along with three known compounds(6-8),were isolated from the whole plants of Chloranthus holostegius.Their structures were elucidated using the spectroscopic methods(IR,UV,HR-ESI-MS,ID and 2D NMR),and their absolute configurations were determined by the X-ray crystallography and ECD calculation.Compounds 1-8 were evaluated for their anti-inflammatory effects on LPS-induced RAW 264.7 macrophage cells.Especially,compound 4 exhibited the most significant anti-inflammatory activity with the secretion levels of TNF-α and IL-6 at 15.52%and 5.98%,respectively,better than that of dexamethasone.
基金supported by the National Key Research and Development Program of China(Nos.2018YFA0903200 and 2018YFA0903201)the National Natural Science Foundation of China(Nos.81925037 and 31900284)+3 种基金the Chang Jiang Scholars Program(Young Scholar)from the Ministry of Education of China(GAO Hao,2017)the National High-level Personnel of Special Support Program(No.2017RA2259)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)K.C.Wong Education Foundation(GAO Hao,2016)。
文摘Biotransformation ofα-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans,(+)(7 S,8 S,7’S,8’R)iso-magnosalicin(1 a)/(-)(7 R,8 R,7’R,8’S)iso-magnosalicin(1 b)and(+)(7 R,8 R,7’S,8’R)magnosalicin(2 a)/(-)(7 S,8 S,7’R,8’S)magnosalicin(2 b),and four known metabolites,(±)acoraminol A(3),(±)acoraminol B(4),asaraldehyde(5),and 2,4,5-trimethoxybenzoic acid(6).Their structures,including absolute configurations,were determined by extensive analysis of NMR spectra,X-ray crystallography,and quantum chemical ECD calculations.The cytotoxic activity and Aβ_(42)aggregation inhibitory activity of all the compounds were evaluated.Compound 2 displayed significant anti-Aβ_(42)aggregation activity with an inhibitory rate of 60.81%(the positive control EGCG:69.17%).In addition the biotransformation pathway ofα-asarone by Alternaria longipes CGMCC 3.2875 was proposed.
基金the National Key R & D Program of China (No. 2018YFC1706200)the National Natural Science Foundation of China (Nos. 81630095, 81622045, and 81803379)+2 种基金the Science & Technology Program of China (No.2019ZX09735002-003)the China Postdoctoral Science Foundation(Nos. 2019T120794, and 2018M633291)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (No. 2017BT01Y036)。
文摘Three new indole alkaloids, flueindolines A–C(1–3), along with nine known alkaloids(4–12), were isolated from the fruits of Flueggea virosa(Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indole alkaloids possessing an unusual pyrido[1, 2-a]indole framework, and 3 presents a rare spiro(pyrrolizidinyl-oxindole) backbone. Their structures with absolute configurations were elucidated by means of comprehensive spectroscopic analysis, chemical calculation, as well as X-ray crystallography. Chiral resolution and absolute configuration determination of the known compounds 4, 10, and 11 were reported for the first time. The hypothetical biogenetical pathways of 1–3 were herein also proposed.
基金This work was financially supported by grants from National Key Research and Development Program of China(2018YFA0903200,2018YFA0903201)the National Natural Science Foundation of China(32170060,31870032).
文摘Triterpenes are derived from squalene or oxidosqualene.However,a new class of triterpenes derived from hexaprenyl pyrophosphate has been recently discovered,formed by a new family of chimeric class I triterpene synthases.The cyclization mechanisms of triterpenes were elucidated by isotopic labeling and protein structural analyses,which helps understand the biosynthesis of triterpenes in nature.
基金supported by the National Key Research and Development Program of China(No.2018YFA0903200//2018YFA0903201)the National Natural Science Foundation of China(Nos.81925037 and 81973213)+6 种基金National High-level Personnel of Special Support Program(No.2017RA2259)the 111 Project of Ministry of Education of the People's Republic of China(No.B13038)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)Guangdong International Science and Technology Cooperation Base(No.2021A0505020015)Innovative and Research Teams Project of Guangdong Higher Education Institution(No.2021KCXTD001)K.C.Wong Education Foundation(No.Guo-Dong Chen,2021,China)the Science and Technology Planning Project of Guangzhou(No.202201020048)。
文摘From the fungus Trichoderma sp., we isolated seven novel 18-residue peptaibols, neoatroviridins E-K ( 1−7 ), and six new 14-residue peptaibols, harzianins NPDG J-O ( 8−13 ). Additionally, four previously characterized 18-residue peptaibols neoatroviridins A-D ( 14−17 ) were also identified. The structural configurations of the newly identified peptaibols ( 1−13 ) were determined by comprehensive nuclear magnetic resonance (NMR) and high-resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS/MS) data. Their absolute configurations were further determined using Marfey’s method. Notably, compounds 12 and 13 represent the first 14-residue peptaibols containing an acidic amino acid residue. In antimicrobial assessments, all 18-residue peptaibols ( 1 − 7 , 14 − 17 ) exhibited moderate inhibitory activities against Staphylococcus aureus 209P, with minimum inhibitory concentration (MIC) values ranging from 8−32 μg·mL^(−1). Moreover, compound 9 exhibited moderate inhibitory effect on Candida albicans FIM709, with a MIC value of 16 μg·mL^(−1).
基金supported by the National Natural Science Foundation of China(Nos.81602984 and 81630097)Science and Technology Planning Project of Guangdong Province(No.2015B030301005)
文摘The flower buds of Lonicera macranthoides(Shan Yin-Hua), represent an important traditional Chinese medicine and food ingredient. A phytochemical investigation of the 70% EtOH extract of the flower buds of L. macranthoides resulted in the isolation of 12 triterpenoids(1-12), including two new ursane-type nortriterpenes, 2α, 24-dihydroxy-23-nor-ursolic acid(1) and 2α, 4α-dihydroxy-23-nor-ursolic acid(2). Their structures were established by multiple spectroscopic methods and comparison with literature data. All isolated compounds were evaluated for their anti-inflammatory effects in LPS-activated RAW264.7 cells. Compounds 1 and 2 exhibited inhibitory effects on iNOS at the concentration of 30 μmol·L^(-1).
基金supported by grants from the National Natural Science Foundation of China(Nos.81803376,82074116,81973190)the Guangdong Basic and Applied Basic Research Foundation(No.2020B1515020033)+3 种基金the Natural Science Foundation of Guangdong Province(No.2018B030311020)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)the Guangdong Basic and Applied Basic Research Foundation-Regional Joint Fund(Youth Fund Project,No.2020A1515110415)the high performance public computing service platform of Ji nan Un iversity.
文摘Sophaloseedlines A-G(1-7),seven new matrine-based alkaloids along with two known analogues,were isolated from the seeds of Sophora alopecuroides.The new structures were determined based on extensive spectroscopic data,electronic circular dichroism calculations,and X-ray crystallography.Notably,sophaloseedline A(1)represents a novel rearranged 6(5→17)-abeo-matrine alkaloid featuring unprecedented highly constructed 7/6/5/6 tetracyclic fused ring skeleton.The hypothetical biosynthetic pathways for sophaloseedli nes A-F were proposed based on co-existing precursors.Additionally,all the isolated alkaloids were screened for their antiviral activities against hepatitis B virus,and new alkaloids 1 and 2 displayed more potent activities than those of matrine(a parent alkaloid of title plant)and positive control(lamivudine).
基金This project was supported financially by grants from the National Natural Science Foundation of China(Nos.81803376,82074116,81973190)the Guangdong Basic and Applied Basic Research Foundation(No.2020B1515020033)+4 种基金the Natural Science Foundation of Guangdong Province(No.2018B030311020)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)Guangdong Basic and Applied Basic Research Foundation-Regional Joint Fund(Youth Fund Project,No.2020A1515110415)Pearl River S&T Nova Program of Guangzhou(No.201906010069)We thank the High Performance Public Computing Service Platform of Jinan University for the help of theoretical ECD calculations.
文摘A phytochemical investigation on the seeds of Sophora alopecuroides led to obtaining fourteen structurally diverse matrine-based alkaloids(1-14),including eight new ones(1,6,8-12,14).Notably,alopecuroide F(1)represents the first dimeric matrine-type skeleton assembled via unprecedent C-13-C-12'connection.The new structures were determined through extensive spectroscopic data(UV,OR,HRESIMS,1D,and 2D NMR),ECD calculations,and three instances,verified by X-ray crystallography.Biologically,all alkaloids were evaluated for cytotoxicity against four human cancer cell lines(HepG2,A549,THP-1,and MCF-7)and anti-inflammatory activities for two pro-inflammatory cytokines(TNF-αand IL-6).Alopecuroide F(1)can inhibit TNF-αand IL-6 productions in a dose-dependent manner with IC50 values of 35.6±0.5 and 41.7±0.8μmol/L,respectively.
基金supported by the Program for Changjiang Scholars and Innovative Research Team in the University(No.IRT0965)the Team Project of Natural Science Foundation of Guangdong Province(No.8351063201000003)the Science and Technology Planning Project of Guangdong Province(No.2012A080204005)
文摘AIM:To investigate the chemical constituents of Vitex negundo.METHOD:Compounds were isolated by different chromatographic methods and their structures were elucidated on the basis of NMR spectroscopy.RESULTS:Four compounds were isolated and identified as 2α,3α,24-trihydroxyurs-12,20(30)-dien-28-oic acid-28-O-β-D-glucopyranosyl ester(1),corosolic acid(2),vulgarsaponin A(3) and 2α,3α,24-trihydroxyurs-12-en-28-oic acid-28-O-β-Dglucopyranosyl ester(4),respectively.CONCLUSION:Compound 1 is a new triterpenoid glycoside.
基金financially supported by grants from National Key Research and Development Program of China(2018YF A0903200/2018YFA0903201)the National Natural Science Foundation of China(81925037 and 81973213)+5 种基金Chang Jiang Scholars Program(Young Scholar)from the Ministry of Education of China(Hao Gao,2017)National High-level Personnel of Special Support Program(2017RA2259,China)the 111 Project of Ministry of Education of the People’s Republic of China(B13038)the Guangdong Natural Science Funds for Distinguished Young Scholar(2017A03036027,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y036,China)K.C.Wong Education Foundation(Hao Gao,2016,China)。
文摘A chemical investigation on Sporormiella sp.led to the isolation and structural elucidation of tripodalsporormielones Ae C(1-3),a new class of polyketide possessing unprecedented cage-like skeletons with polyvdent bridged and fused ring systems.These polyketides with cage-like skeletons were characterized as a high non-protonated carbon-containing system,which resulted in few HMBC correlations observed and made the accurate structures hard to be obtained by NMR.Especially,some signals of non-protonated sp;carbons are weak and even unobservable in compound 1.In order to establish the structure of 1,the calculated NMR with DP4 evaluation was applied to determine the structure from the plausible structure candidates obtained from the detailed NMR analysis.Based on NMR experiments and calculated NMR,the structures of isolated compounds were established and confirmed by X-ray technology.Through chiral isolation,the optically pure enantiomers of 1 and 3 were obtained,and their absolute configurations were determined based on ECD quantum chemical calculation.Based on the isolated compounds and our previous work,1-3 would be derived from 3-methylorcinaldehyde,and their plausible biosynthetic mechanism was proposed.Furthermore,1 exhibited obvious short-term memory improvement activity on an Alzheimer’s disease fly model.
