[2+2]-Type cyclobutane derivatives comprise a large family of natural products with diverse molecular architectures.However,the structure elucidation of the cyclobutane ring,including its connection mode and stereoche...[2+2]-Type cyclobutane derivatives comprise a large family of natural products with diverse molecular architectures.However,the structure elucidation of the cyclobutane ring,including its connection mode and stereochemistry,presents a significant challenge.Plumerubradins A-C(1-3),three novel iridoid glycoside[2+2]dimers featuring a highly functionalized cyclobutane core and multiple stereogenic centers,were isolated from the flowers of Plumeria rubra.Through biomimetic semisynthesis and chemical degradation of compounds 1-3,synthesis of phenylpropanoid-derived[2+2]dimers 7-10,combined with extensive spectroscopic analysis,single-crystal X-ray crystallography,and microcrystal electron diffraction experiments,the structures with absolute configurations of 1-3 were unequivocally elucidated.Furthermore,quantum mechanics-based^(1)H NMR iterative full spin analysis successfully established the correlations between the signal patterns of cyclobutane protons and the structural information of the cyclobutane ring in phenylpropanoid-derived[2+2]dimers,providing a diagnostic tool for the rapid structural elucidation of[2+2]-type cyclobutane derivatives.展开更多
To investigate the cembranoid diterpenes from the soft coral Sarcophyton sp. collected in the South China Sea. Repeatedly column chromatography was performed for the isolation and purification. The structures were elu...To investigate the cembranoid diterpenes from the soft coral Sarcophyton sp. collected in the South China Sea. Repeatedly column chromatography was performed for the isolation and purification. The structures were elucidated on the basis of extensive spectral data （IR, MS, 1 D- and 2D-NMR） analysis by comparing with literature data. A new cembranoid diterpene namely sarcophyolide A （1）, together with 7a, 8β-dihydroxydeepoxysarcophine （2） were isolated from this species. The cembranoid diterpenes with 7-1actone could be chemotaxonomic markers of Sarcophyton sp.展开更多
As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons underg...As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, ＇plastic＇ neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.展开更多
The structures of two novel lactams isolated from Clausena lansium were elucidated mainly on the bases of their spectral data. They are homoclausenamide(1),a -lactam,and zetaclausenamide(4), an eight-membered ring lac...The structures of two novel lactams isolated from Clausena lansium were elucidated mainly on the bases of their spectral data. They are homoclausenamide(1),a -lactam,and zetaclausenamide(4), an eight-membered ring lactam.展开更多
A novel and unusual sterol with unsaturation in the△^(5(14)) position,5α-cholesta-8(14),24(25)-diene-3β,6α-diol 1,was isolated from the South China Ses sponge Dysidea sp.The structure and relative stereochemistry ...A novel and unusual sterol with unsaturation in the△^(5(14)) position,5α-cholesta-8(14),24(25)-diene-3β,6α-diol 1,was isolated from the South China Ses sponge Dysidea sp.The structure and relative stereochemistry of 1 was established by spectral analysis and comparison to the spectral data of known sterols.展开更多
A new prenylated flavonol, maackiaflavonol, was isolated from the ethanol extract of the roots of Maackia tenuifolia. Its structure was elucidated as 7-hydrox-8-prenylflavonol by means of spectroscopic analysis (UV, I...A new prenylated flavonol, maackiaflavonol, was isolated from the ethanol extract of the roots of Maackia tenuifolia. Its structure was elucidated as 7-hydrox-8-prenylflavonol by means of spectroscopic analysis (UV, IR, MS, NMR and 1H-1H COSY) and confirmed by total synthesis.展开更多
A new p-acetylphenyl glycoside,asterbatanoside A has been isolated from the roots of Aster batangensis, and its structure has been elucidated as p-hydroxyacetophenone- -O-α-D-xylopyranosyl-(1,6) -β-D-glucopyranosid...A new p-acetylphenyl glycoside,asterbatanoside A has been isolated from the roots of Aster batangensis, and its structure has been elucidated as p-hydroxyacetophenone- -O-α-D-xylopyranosyl-(1,6) -β-D-glucopyranoside by chemical and spectral means.For the confirmation of this structure. the synthesis of this compound was also reported in this paper.展开更多
On the basis of spectroscopic evidence (MS, ~1HNMR, ^(13)CNMR, CD, ~1H-~1H and ~1H-^(13)C cosy NMR) and chemical synthesis, the structure of isodopharicin E (1), isolated from the dry leaves and tender branches of Iso...On the basis of spectroscopic evidence (MS, ~1HNMR, ^(13)CNMR, CD, ~1H-~1H and ~1H-^(13)C cosy NMR) and chemical synthesis, the structure of isodopharicin E (1), isolated from the dry leaves and tender branches of Isodon pharicus (Prain) Murata was elucidated as 3R, 3'R, 13S, 13'S-tetrahydroxy-11S, 11'S-diacetoxy(16S-O-15')-bisentkaur-15'-en-15-one.展开更多
The spectral data and chemical properties of two new amides isolated from Clausena lansium led to the assignment of acyclic structures of C-6 and C-7. The absolute configurations of the two chiral carbons in C-6 were ...The spectral data and chemical properties of two new amides isolated from Clausena lansium led to the assignment of acyclic structures of C-6 and C-7. The absolute configurations of the two chiral carbons in C-6 were determined by degradation to be 3S4R.展开更多
The fruit of Camptotheca acuminate is used as a traditional Chinese medicine.Eight compounds were isolated from the fruit of Camptotheca acuminate for the first time,including(+)-(S)-abscisic acid(1),blumenol A(2),(E)...The fruit of Camptotheca acuminate is used as a traditional Chinese medicine.Eight compounds were isolated from the fruit of Camptotheca acuminate for the first time,including(+)-(S)-abscisic acid(1),blumenol A(2),(E)-3-hydroxymegastigm-7-en-9-one(3),(-)-(3R)-3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin(4),(-)-(3R)-8-methoxy-3-methyl-3,4-dihydro-1H-isochromen-1-one(5),neocnidilide(6),(3S)-butylphthalide(7)and senkyunolide I(8).Their structures were determined by comprehensive spectroscopic methods,including HRESIMS and 1D NMR.展开更多
Although anisotropic NMR spectroscopy has emerged as a powerful method for determining the relative configuration of complex natural products,major challenges persist with structurally flexible molecules.In this study...Although anisotropic NMR spectroscopy has emerged as a powerful method for determining the relative configuration of complex natural products,major challenges persist with structurally flexible molecules.In this study,we conducted a system-atic comparative analysis of stereochemical elucidation,combining anisotropic NMR spectroscopy and density functional theory(DFT)calculations on spiroepicoccin B(1)and epicoccin V(2),which were characterized as thiodiketopiperazine marine natural products isolated from the deep-sea-derived fungus Epicoccum nigrum SD-388.For the flexible compound 2,we compared various conformational sampling approaches,including an assessment of the quality of relative energies within the obtained ensembles.We demonstrated the critical role of dispersion correction within DFT computations to precisely account for weak non-bonded intramolecular interactions.By integrating anisotropic NMR analysis,chemical shifts,elec-tronic circular dichroism,and DFT computations,we determined the absolute configurations and conformational ensembles for 1 and 2,respectively,highlighting the significance of the intramolecular methyl-πinteraction in stabilizing one of the conformers.Our study introduces new strategies to address conformational flexibility in the stereochemical elucidation of challenging organic molecules.展开更多
A pair of coumarin-based polycyclic meroterpenoid enantiomers(+)/(-)-gerbeloid A[(+)-1a and(-)-1b]were isolated from the medicinal plant Gerbera piloselloides,which have a unique caged oxatricyclo[4.2.2.0^(3,8)]decene...A pair of coumarin-based polycyclic meroterpenoid enantiomers(+)/(-)-gerbeloid A[(+)-1a and(-)-1b]were isolated from the medicinal plant Gerbera piloselloides,which have a unique caged oxatricyclo[4.2.2.0^(3,8)]decene scaffold.Their planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction analysis.Guided by the hypothetical biosynthetic pathway,the biomimetic synthesis of racemic 1 was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material via oxa-6πelectrocyclization and intramolecular[2+2]photocycloaddition.Subsequently,the results of the biological activity assay demonstrated that both(+)-1a and(-)-1b exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish model.Notably,the lipid-lowering activity of(+)-1a is better than that of(-)-1b at the same concentration,and molecular mechanism study has shown that(+)-1a and(-)-1b impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBPα/PPARγsignaling and Perilipin signaling in vitro and in vivo.Our findings provide a promising drug model molecule for the treatment of obesity.展开更多
The Plectranthinae clade,which includes genera such as Plectranthus,Ocimum,and Aeollanthus,is well known for its diverse array of diterpenoids.While numerous studies have deepened the understanding of diterpene divers...The Plectranthinae clade,which includes genera such as Plectranthus,Ocimum,and Aeollanthus,is well known for its diverse array of diterpenoids.While numerous studies have deepened the understanding of diterpene diversity across the clade,Aeollanthus species remain underexplored,with only two studies focusing on their diterpene profiles.The NMR-based chemical profiling of the EtOAc leaf extract of the rocky and succulent species Aeollanthus buchnerianus Briq.reveals a range of diterpenes with isopimarane and abietane skeletons including several previously unreported analogues.Interestingly,the isolated compounds provided insights into the breakdown patterns of both diterpene classes by examining the product ions in their MS2 spectra.These data offer valuable information for evaluating the taxonomic position of this species in relation to other species within the clade.展开更多
Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin...Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system,while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system.Their structures were established by extensive spectroscopic analysis,X-ray crystallography,and computational methods.The plausible biosynthetic routes for the compounds were also proposed.In oleic acid(OA)-induced HepG2 cells,all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8μmol/L.Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.展开更多
Network pharmacology has gained widespread application in drug discovery,particularly in traditional Chinese medicine(TCM)research,which is characterized by its“multi-component,multi-target,and multi-pathway”nature....Network pharmacology has gained widespread application in drug discovery,particularly in traditional Chinese medicine(TCM)research,which is characterized by its“multi-component,multi-target,and multi-pathway”nature.Through the integration of network biology,TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms,establishing a novel research paradigm for TCM modernization.The rapid advancement of machine learning,particularly revolutionary deep learning methods,has substantially enhanced artificial intelligence(AI)technology,offering significant potential to advance TCM network pharmacology research.This paper describes the methodology of TCM network pharmacology,encompassing ingredient identification,network construction,network analysis,and experimental validation.Furthermore,it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods.Finally,it addresses challenges and future directions regarding cell-cell communication(CCC)-based network construction,analysis,and validation,providing valuable insights for TCM network pharmacology.展开更多
(±)-Talapyrones A−F(1−6),six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems,were isolated from the fungus Talaromyces adpressus.Their structures were determined by spectr...(±)-Talapyrones A−F(1−6),six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems,were isolated from the fungus Talaromyces adpressus.Their structures were determined by spectroscopic analysis and HR-ESI-MS data,and their absolute configurations were elucidated using a modified Mosher’s method and electronic circular dichroism(ECD)calculations.(±)-Talapyrones A−F(1−6)possess a 6/6/6 tricyclic skeleton,presumably formed through a Michael addition reaction between one molecule ofα-pyrone derivative and one molecule of C8 poly-β-keto chain.In addition,compounds 2/3 and 4/5 are two pairs of C-18 epimers,respectively.Putative biosynthetic pathways of 1−6 were discussed.展开更多
Five novel emestrin-type epipolythiodioxopiperazines(ETPs),prenylemestrins C-G(1-5),along with two known ETPs,prenylemestrin A(6)and prenylemestrin B(7),were obtained from Aspergillus nidulans.Their structures were ch...Five novel emestrin-type epipolythiodioxopiperazines(ETPs),prenylemestrins C-G(1-5),along with two known ETPs,prenylemestrin A(6)and prenylemestrin B(7),were obtained from Aspergillus nidulans.Their structures were characterized by spectroscopic data,X-ray crystallographic data,ECD comparisons and calculations.Prenylemestrins C-G(1-5)represent a rare class of ETPs,characterized by a 2,5-dithia-7,9-diazabicyclo[4.2.2]decane-8,10-dione core involving a hemiterpene moiety.Notably,compound 6 exhibited moderate cytotoxicity,inducing G2/M cell cycle arrest and apoptosis of L1210 cells by regulating the PI3K/AKT signaling pathway and mitochondrial apoptotic mechanisms.展开更多
A chemical investigation of secondary metabolites(SMs)from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine(DKP)-diphenyl ether hybrids,designated as diphenylemestrins A-E(1-5).These c...A chemical investigation of secondary metabolites(SMs)from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine(DKP)-diphenyl ether hybrids,designated as diphenylemestrins A-E(1-5).These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures,with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component.The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism(ECD)calculations.Notably,diphenylemestrin C(3)exhibited moderate cytostatic activity against NB4 cells,with a half maximal inhibitory concentration(IC50)value of 21.99μmol·L-1,and induced apoptosis at higher concentrations.展开更多
The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum(I.dunnianum)resulted in the isolation of five pairs of new lignans(1–5),and 7 known analogs(6–12).The separation of enantiomer mi...The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum(I.dunnianum)resulted in the isolation of five pairs of new lignans(1–5),and 7 known analogs(6–12).The separation of enantiomer mixtures 1–5 to 1a/1b–5a/5b was achieved using a chiral column with acetonitrile−water mixtures as eluents.The planar structures of 1–2 were previously undescribed,and the chiral separation and absolute configurations of 3–5 were reported for the first time.Their structures were determined through comprehensive spectroscopic data analysis[nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass(HR-ESI-MS),infrared(IR),and ultraviolet(UV)]and quantum chemistry calculations(ECD).The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide(LPS)-stimulated BV-2 cells.Compounds 1a,3a,3b,and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner.Western blot and real-time polymerase chain reaction(PCR)assays revealed that 1a down-regulated the messenger ribonucleic acid(mRNA)levels of tumor necrosis factorα(TNF-α),interleukin-6(IL-6),COX-2,and iNOS and the protein expressions of COX-2 and iNOS.This research provides guidance and evidence for the further development and utilization of I.dunnianum.展开更多
基金supported by the National Key R&D Program of China(No.2023YFC3503902)the National Natural Science Foundation of China(Nos.82293681(82293680)and 82321004)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(Nos.2022B1515120015 and 2021A1515111021)the Guangdong Major Project of Basic and Applied Basic Research(No.2023B0303000026)the Science and Technology Projects in Guangzhou(No.202102070001).
文摘[2+2]-Type cyclobutane derivatives comprise a large family of natural products with diverse molecular architectures.However,the structure elucidation of the cyclobutane ring,including its connection mode and stereochemistry,presents a significant challenge.Plumerubradins A-C(1-3),three novel iridoid glycoside[2+2]dimers featuring a highly functionalized cyclobutane core and multiple stereogenic centers,were isolated from the flowers of Plumeria rubra.Through biomimetic semisynthesis and chemical degradation of compounds 1-3,synthesis of phenylpropanoid-derived[2+2]dimers 7-10,combined with extensive spectroscopic analysis,single-crystal X-ray crystallography,and microcrystal electron diffraction experiments,the structures with absolute configurations of 1-3 were unequivocally elucidated.Furthermore,quantum mechanics-based^(1)H NMR iterative full spin analysis successfully established the correlations between the signal patterns of cyclobutane protons and the structural information of the cyclobutane ring in phenylpropanoid-derived[2+2]dimers,providing a diagnostic tool for the rapid structural elucidation of[2+2]-type cyclobutane derivatives.
基金National Natural Science Foundation of China(Grant No.30672607)the National Hi-Tech Projects(Grant No.2006AA09Z446,2006DFA31100 and 2006AA09Z405)+1 种基金China Uni-PhD Base Project(Grant No.20060001149)International Cooperation Projects of BMBF-MOST.
文摘To investigate the cembranoid diterpenes from the soft coral Sarcophyton sp. collected in the South China Sea. Repeatedly column chromatography was performed for the isolation and purification. The structures were elucidated on the basis of extensive spectral data （IR, MS, 1 D- and 2D-NMR） analysis by comparing with literature data. A new cembranoid diterpene namely sarcophyolide A （1）, together with 7a, 8β-dihydroxydeepoxysarcophine （2） were isolated from this species. The cembranoid diterpenes with 7-1actone could be chemotaxonomic markers of Sarcophyton sp.
基金supported by grant SDU2020 to Prof.Bente Finsen and Prof.Martin R.Larsen(COPING AD–Collaborative Project on the Interaction between Neurons and Glia in Alzheimer’s Disease)
文摘As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, ＇plastic＇ neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.
文摘The structures of two novel lactams isolated from Clausena lansium were elucidated mainly on the bases of their spectral data. They are homoclausenamide(1),a -lactam,and zetaclausenamide(4), an eight-membered ring lactam.
文摘A novel and unusual sterol with unsaturation in the△^(5(14)) position,5α-cholesta-8(14),24(25)-diene-3β,6α-diol 1,was isolated from the South China Ses sponge Dysidea sp.The structure and relative stereochemistry of 1 was established by spectral analysis and comparison to the spectral data of known sterols.
文摘A new prenylated flavonol, maackiaflavonol, was isolated from the ethanol extract of the roots of Maackia tenuifolia. Its structure was elucidated as 7-hydrox-8-prenylflavonol by means of spectroscopic analysis (UV, IR, MS, NMR and 1H-1H COSY) and confirmed by total synthesis.
文摘A new p-acetylphenyl glycoside,asterbatanoside A has been isolated from the roots of Aster batangensis, and its structure has been elucidated as p-hydroxyacetophenone- -O-α-D-xylopyranosyl-(1,6) -β-D-glucopyranoside by chemical and spectral means.For the confirmation of this structure. the synthesis of this compound was also reported in this paper.
文摘On the basis of spectroscopic evidence (MS, ~1HNMR, ^(13)CNMR, CD, ~1H-~1H and ~1H-^(13)C cosy NMR) and chemical synthesis, the structure of isodopharicin E (1), isolated from the dry leaves and tender branches of Isodon pharicus (Prain) Murata was elucidated as 3R, 3'R, 13S, 13'S-tetrahydroxy-11S, 11'S-diacetoxy(16S-O-15')-bisentkaur-15'-en-15-one.
文摘The spectral data and chemical properties of two new amides isolated from Clausena lansium led to the assignment of acyclic structures of C-6 and C-7. The absolute configurations of the two chiral carbons in C-6 were determined by degradation to be 3S4R.
文摘The fruit of Camptotheca acuminate is used as a traditional Chinese medicine.Eight compounds were isolated from the fruit of Camptotheca acuminate for the first time,including(+)-(S)-abscisic acid(1),blumenol A(2),(E)-3-hydroxymegastigm-7-en-9-one(3),(-)-(3R)-3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin(4),(-)-(3R)-8-methoxy-3-methyl-3,4-dihydro-1H-isochromen-1-one(5),neocnidilide(6),(3S)-butylphthalide(7)and senkyunolide I(8).Their structures were determined by comprehensive spectroscopic methods,including HRESIMS and 1D NMR.
基金supported by the Leibniz-Forschungsinstitut für Molekulare Pharmakologie(FMP)and the Deutsche Forschungsgemeinschaft(DFG,German Research Foun-dation)under RTG 2473 Bioactive Peptides(392923329)A.F.K.and H.S.under Germany’s Excellence Strategy-EXC 2008/1(UniSysCat,390540038)to C.J.S.and H.S.+2 种基金the National Natural Science Foundation of China(U2006203)to B.-G.W.X.-L.Lsupport from the Taishan Scholars Program(tsqn202306366,China).A.N.-Vthanks National Council for Scien-tific and Technological Development(CNPq)for a research fellowship(309873/2023-1).
文摘Although anisotropic NMR spectroscopy has emerged as a powerful method for determining the relative configuration of complex natural products,major challenges persist with structurally flexible molecules.In this study,we conducted a system-atic comparative analysis of stereochemical elucidation,combining anisotropic NMR spectroscopy and density functional theory(DFT)calculations on spiroepicoccin B(1)and epicoccin V(2),which were characterized as thiodiketopiperazine marine natural products isolated from the deep-sea-derived fungus Epicoccum nigrum SD-388.For the flexible compound 2,we compared various conformational sampling approaches,including an assessment of the quality of relative energies within the obtained ensembles.We demonstrated the critical role of dispersion correction within DFT computations to precisely account for weak non-bonded intramolecular interactions.By integrating anisotropic NMR analysis,chemical shifts,elec-tronic circular dichroism,and DFT computations,we determined the absolute configurations and conformational ensembles for 1 and 2,respectively,highlighting the significance of the intramolecular methyl-πinteraction in stabilizing one of the conformers.Our study introduces new strategies to address conformational flexibility in the stereochemical elucidation of challenging organic molecules.
基金support from the Natural Sciences Foundation of China(82374035)the CAMS Innovation Fund for Medical Sciences(CIFMS,2022-I2M-1-017,China).
文摘A pair of coumarin-based polycyclic meroterpenoid enantiomers(+)/(-)-gerbeloid A[(+)-1a and(-)-1b]were isolated from the medicinal plant Gerbera piloselloides,which have a unique caged oxatricyclo[4.2.2.0^(3,8)]decene scaffold.Their planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction analysis.Guided by the hypothetical biosynthetic pathway,the biomimetic synthesis of racemic 1 was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material via oxa-6πelectrocyclization and intramolecular[2+2]photocycloaddition.Subsequently,the results of the biological activity assay demonstrated that both(+)-1a and(-)-1b exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish model.Notably,the lipid-lowering activity of(+)-1a is better than that of(-)-1b at the same concentration,and molecular mechanism study has shown that(+)-1a and(-)-1b impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBPα/PPARγsignaling and Perilipin signaling in vitro and in vivo.Our findings provide a promising drug model molecule for the treatment of obesity.
基金funded by a grant to MSJS from Procter and Gamble.
文摘The Plectranthinae clade,which includes genera such as Plectranthus,Ocimum,and Aeollanthus,is well known for its diverse array of diterpenoids.While numerous studies have deepened the understanding of diterpene diversity across the clade,Aeollanthus species remain underexplored,with only two studies focusing on their diterpene profiles.The NMR-based chemical profiling of the EtOAc leaf extract of the rocky and succulent species Aeollanthus buchnerianus Briq.reveals a range of diterpenes with isopimarane and abietane skeletons including several previously unreported analogues.Interestingly,the isolated compounds provided insights into the breakdown patterns of both diterpene classes by examining the product ions in their MS2 spectra.These data offer valuable information for evaluating the taxonomic position of this species in relation to other species within the clade.
基金financially supported by the National Natural Science Foundation of China(Nos.32270413,82060631,82160808,and 82360035)the Science and Technology Department of Guizhou Province(Nos.QKHJC 2020–1Z076,QKHJC-ZK[2023]YB156,QKHJC-ZK[2021]YB569,and QKHPTRC[2020]5008)+4 种基金Excellent Young Talents Plan of Guizhou Medical University(2023,No.106)the 13thbatch of outstanding young scientific and technological talents in Guizhou Province(No.QKHPTRC[2021]5633)Guizhou Science and Technology Innovation Talent Team(No.QKHPTRC–CXTD[2022]007)High-level Innovative Talents in Guizhou Province(Thousand Levels of Talent for Chunmao Yuan in 2018)the project of State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University(Nos.FAMP202102K and QJJ[2023]113)。
文摘Hymoins A–C(1–3),three unusual polycyclic polyprenylated acylphloroglucinols(PPAPs)were isolated from the flowers of Hypericum monogynum.Hymoin A features the first intriguing 6/5/5/5/7 pentacyclic caged PPAP.Hymoin B is characterized by an unprecedented rearranged 5/6/8 tricyclic ring system,while hymoin C represents the first rearranged PPAP with a fantastic spirocyclic 5/6/7 ring system.Their structures were established by extensive spectroscopic analysis,X-ray crystallography,and computational methods.The plausible biosynthetic routes for the compounds were also proposed.In oleic acid(OA)-induced HepG2 cells,all compounds exhibited significant lipid-lowering activity at the concentrations of 2–8μmol/L.Further mechanistic study implied that compound 1 exhibited excellent lipid-lowering activity in OA-induced HepG2 cells through inhibiting the proteins of free fatty acids synthesis and improving lipidolysis.
基金supported by the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(No.2024C03106,X.F.)the National Natural Science Foundation of China(No.82474160,X.S.)+2 种基金the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LBZ24H270001,X.P.)the Major Joint Projects Supported by the National Administration of TCM and Zhejiang Province(No.GZY-ZI-KJ-23037,X.P.)the Ningbo Top Medical and Health Research Program(No.2022030309,X.P.)。
文摘Network pharmacology has gained widespread application in drug discovery,particularly in traditional Chinese medicine(TCM)research,which is characterized by its“multi-component,multi-target,and multi-pathway”nature.Through the integration of network biology,TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms,establishing a novel research paradigm for TCM modernization.The rapid advancement of machine learning,particularly revolutionary deep learning methods,has substantially enhanced artificial intelligence(AI)technology,offering significant potential to advance TCM network pharmacology research.This paper describes the methodology of TCM network pharmacology,encompassing ingredient identification,network construction,network analysis,and experimental validation.Furthermore,it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods.Finally,it addresses challenges and future directions regarding cell-cell communication(CCC)-based network construction,analysis,and validation,providing valuable insights for TCM network pharmacology.
基金supported by the National Key Research and Development Program of China(No.2021YFA0910500)the National Natural Science Foundation of China(Nos.U22A20380,82173706,and 82104028)the Science and Technology Major Project of Hubei Province(No.2021ACA012).
文摘(±)-Talapyrones A−F(1−6),six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems,were isolated from the fungus Talaromyces adpressus.Their structures were determined by spectroscopic analysis and HR-ESI-MS data,and their absolute configurations were elucidated using a modified Mosher’s method and electronic circular dichroism(ECD)calculations.(±)-Talapyrones A−F(1−6)possess a 6/6/6 tricyclic skeleton,presumably formed through a Michael addition reaction between one molecule ofα-pyrone derivative and one molecule of C8 poly-β-keto chain.In addition,compounds 2/3 and 4/5 are two pairs of C-18 epimers,respectively.Putative biosynthetic pathways of 1−6 were discussed.
基金National Natural Science Foundation of China(U22A20380,82173706,82104028)Fundamental Research Funds for the Central Universities(2024BRA018)financially supported this project.
文摘Five novel emestrin-type epipolythiodioxopiperazines(ETPs),prenylemestrins C-G(1-5),along with two known ETPs,prenylemestrin A(6)and prenylemestrin B(7),were obtained from Aspergillus nidulans.Their structures were characterized by spectroscopic data,X-ray crystallographic data,ECD comparisons and calculations.Prenylemestrins C-G(1-5)represent a rare class of ETPs,characterized by a 2,5-dithia-7,9-diazabicyclo[4.2.2]decane-8,10-dione core involving a hemiterpene moiety.Notably,compound 6 exhibited moderate cytotoxicity,inducing G2/M cell cycle arrest and apoptosis of L1210 cells by regulating the PI3K/AKT signaling pathway and mitochondrial apoptotic mechanisms.
基金The National Key Research and Development Program of China(No.2021YFA0910500)the National Natural Science Foundation of China(Nos.U22A20380,82104028,82173706,and 82373755)+1 种基金the Science and Technology Major Project of Hubei Province(No.2021ACA012)the Fundamental Research Funds for the Central Universities,HUST(No.2021JYCXJJ058)。
文摘A chemical investigation of secondary metabolites(SMs)from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine(DKP)-diphenyl ether hybrids,designated as diphenylemestrins A-E(1-5).These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures,with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component.The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism(ECD)calculations.Notably,diphenylemestrin C(3)exhibited moderate cytostatic activity against NB4 cells,with a half maximal inhibitory concentration(IC50)value of 21.99μmol·L-1,and induced apoptosis at higher concentrations.
基金supported by the Basic Research Program of the Natural Science Fund-Frontier Leading Technology Basic Research Special Project(No.SBK2023050003)by the University Science and Technology Innovation Team of Department of Education of Guizhou Province(No.QJ[2023]099).
文摘The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum(I.dunnianum)resulted in the isolation of five pairs of new lignans(1–5),and 7 known analogs(6–12).The separation of enantiomer mixtures 1–5 to 1a/1b–5a/5b was achieved using a chiral column with acetonitrile−water mixtures as eluents.The planar structures of 1–2 were previously undescribed,and the chiral separation and absolute configurations of 3–5 were reported for the first time.Their structures were determined through comprehensive spectroscopic data analysis[nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass(HR-ESI-MS),infrared(IR),and ultraviolet(UV)]and quantum chemistry calculations(ECD).The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide(LPS)-stimulated BV-2 cells.Compounds 1a,3a,3b,and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner.Western blot and real-time polymerase chain reaction(PCR)assays revealed that 1a down-regulated the messenger ribonucleic acid(mRNA)levels of tumor necrosis factorα(TNF-α),interleukin-6(IL-6),COX-2,and iNOS and the protein expressions of COX-2 and iNOS.This research provides guidance and evidence for the further development and utilization of I.dunnianum.
