Under the guidance of the approach which integrates molecular networking,MolNetEnhancer and Net-work Annotation Propagation(NAP),daphnaltaicanoids A and B(1 and 2)with unprecedented 9-oxa-tetracyclo[6.6.1.0^(2,6).0^(8...Under the guidance of the approach which integrates molecular networking,MolNetEnhancer and Net-work Annotation Propagation(NAP),daphnaltaicanoids A and B(1 and 2)with unprecedented 9-oxa-tetracyclo[6.6.1.0^(2,6).0^(8,13)]pentadecane and tetracyclo[5.3.0.1^(2,5).2^(4,11)]tridecane central frameworks were iso-lated from Daphne altaica Pall.,representing two types of unparalleled meroterpenoid cores.Their struc-tures were elucidated by extensive spectroscopic analysis,nuclear magnetic resonance(NMR)calcula-tions,DP4+analysis and electronic circular dichroism(ECD)calculations.The plausible biosynthetic path-ways for 1 and 2 were postulated.Biologically,2 exerted potent neuroprotective activities which were su-perior to trolox at 12.5 and 25μmol/L.Moreover,1 and 2 exhibited more noticeable acetylcholinesterase inhibitory activities than donepezil.Molecular docking simulations were performed to explore the inter-molecular interaction of compounds 1 and 2 with acetylcholinesterase.The bioactivity evaluation results highlight the prospects of 1 and 2 as a novel category of neurological agents.展开更多
Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides,namely,...Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides,namely,asperversiamides A–C(1–3)and asperheptatides A–D(4–7)and an unusual pyrroloindoline-containing new cycloheptapeptide,asperpyrroindotide A(8).The structure of 8 was elucidated by comprehensive spectroscopic data analysis,and its absolute configuration was determined by advanced Marfey’s method.The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized.Additionally,a series of new derivatives(10−19)of asperversiamide A(1)was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra.The preliminary structure−activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.展开更多
The chemical diversity of scleractinian corals is closely related to their physiological,ecological,and evolutionary status,and can be influenced by both genetic background and environmental variables.To investigate i...The chemical diversity of scleractinian corals is closely related to their physiological,ecological,and evolutionary status,and can be influenced by both genetic background and environmental variables.To investigate intraspecific variation in the metabolites of these corals,the metabolomes of four species(Pocillopora meandrina,Seriatopora hystrix,Acropora formosa,and Fungia fungites)from the South China Sea were analyzed using untargeted mass spectrometry-based metabolomics.The results showed that a variety of metabolites,including amino acids,peptides,lipids,and other small molecules,were differentially distributed among the four species,leading to their significant separation in principal component analysis and hierarchical clustering plots.The higher content of storage lipids in branching corals(P.meandrina,S.hystrix,and A.formosa)compared to the solitary coral(F.fungites)may be due to the high densities of zooxanthellae in their tissues.The high content of aromatic amino acids in P.meandrina may help the coral protect against ultraviolet damage and promote growth in shallow seawater,while nitrogen-rich compounds may enable S.hystrix to survive in various challenging environments.The metabolites enriched in F.fungites,including amino acids,dipeptides,phospholipids,and other small molecules,may be related to the composition of the coral's mucus and its life-history,such as its ability to move freely and live solitarily.Studying the chemical diversity of scleractinian corals not only provides insight into their environmental adaptation,but also holds potential for the chemotaxonomy of corals and the discovery of novel bioactive natural products.展开更多
Objective:Lingzhihuang capsule(LZHC)is a natural product that consists of 10 commonly used medicinal plants,and it is used in traditional Chinese medicine to promote people’s overall health.Previously,LZHC was succes...Objective:Lingzhihuang capsule(LZHC)is a natural product that consists of 10 commonly used medicinal plants,and it is used in traditional Chinese medicine to promote people’s overall health.Previously,LZHC was successfully used as adjuvant therapy for treating patients with cancer.However,the chemical constituents of LZHC and their potential biological functions remain unclear.The aim of this study is to investigate the major bioactive compounds in LZHC and predict their pharmacological targets.Methods:The LZHC constituents were putatively identified by ultra-high performance liquid chromatography coupled with timeof-flight mass spectrometry combined with mass spectrometry-based molecular networking.The targets were predicted using SwissTargetPrediction software,and the associated gene ontology and Kyoto encyclopedia of genes and genomes pathways were analyzed using the Database for Annotation,Visualization,and Integrated Discovery.The mass spectrometry-based molecular network and compound-target-pathway network were constructed using Cytoscape 3.8.0 software.Results:We putatively identified 94 compounds of LZHC by mass spectrometry-based molecular networking,including triterpene(the main structural type)and other clusters(ie,flavonoids and organic acids).Our results suggested that multiple pivotal targets were regulated by LZHC,including tumor necrosis factor,nitric oxide synthase 2,glucocorticoid receptor,estrogen receptor,3-oxo-5-alpha-steroid 4-dehydrogenase 2,prostaglandin e2 receptor ep4 subtype,estrogen receptor beta,phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform,mitogen-activated protein kinase 3,and racalpha serine,which are related to signal transduction,positive regulation of transcription from RNA polymerase II promoters,oxidation-reduction processes,inflammatory responses,and other biological processes.Functional annotation of those targets suggested that several signaling pathways may be regulated by LZHC,such as cancer-related proteoglycans,the PI3K-Aktsignaling展开更多
Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer's disease.In this paper,the combined bioassay model of acetylcholinesterase(AC...Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer's disease.In this paper,the combined bioassay model of acetylcholinesterase(AChE)inhibition,1,1-diphenyl-2-picrylhydrazyl(DPPH)free radical scavenging,and Artemi ci larval lethality was used to evaluate the activity and toxicity of 35 n narine fun gal strains from seas around China.Their bioactive constitue nfs were revealed by thin layer chromatography(TLC)autography,bioactivity coupled LC-MS/MS and Global Natural Products Social Molecular Networking(GNPS).The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound,'tacrine;for which the ratio was 89.8%at 200 pig/ml.Six strains displayed both AChE inhibition(inhibition ratios>20%at 200 pg/ml)and DPPH scavenging activity(scavenging ratios>30%at 200 pg/ml)together with low Artemia larval toxicity(lethal rates<12%).TLC autography showed that the fractioned extracts of four strains contained highly diverse and different bioactive constituents,includi ng strains Talaromyces sp.C2\-\,Aspergillus ter re us C23-3,Trichoderma harzianum DLEN2008005,and Penicillium corylophilum TBG1-17.From the most potent sample F-l 1-1-b(derived from Aspergillus tern us C23-3),five AChE inhibitors and seven antioxida nts were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC-MS/MS,and LC-MS/MS coupled with DPPH incubation.Furthermore,with the aid of GNPS,the AChE inhibitors were plausibly annotated as territrem analogues including territrems A-C/D,arisugacin A and an unknown compound 4,and the seven antioxidants were assigned as butyrolactone I.aspernolide E,a phenolic derivative and possibly unknown compounds 8-10 and 12.展开更多
Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines,especially Vernonia amygdalina,a famous nature medicine for the treatment of tonsilliti...Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines,especially Vernonia amygdalina,a famous nature medicine for the treatment of tonsillitis,diabetes,pneumonia.The current study was designed to combine molecular networking(MN)with diagnostic ions for rapid identification ofΔ^(7,9(11))stigmastane-type saponins which were theα-glucosidase inhibitory active substances in V.amygdalina.First,theα-glucosidase inhibitory activities of fiveΔ^(7,9(11))stigmastane-type steroid saponins that were previously isolated were screened,which indicated that theΔ^(7,9(11))stigmastane-type steroid saponin was one of the active constituents responsible for ameliorating diabetes.Furthermore,a strategy was proposed to identify stigmastane-type steroid saponins and verify the plausibility of derived fragmentation pathways by applying MN,MolNetEnhancer and unsupervised substructure annotation(MS2LDA).Based on this strategy,other sevenΔ^(7,9(11))stigmastane-type steroid saponins were identified from this plant.Our research provide scientific evidence for the antidiabetic potential of the steroid saponin-rich extract of V.amygdalina leaf.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82073736,81872766)Science and Technology Planning Project of Liaoning Province(No.2021JH1/10400049)Liaoning revitalization talents program(Nos.XLYC2002066,XLYC2007180).
文摘Under the guidance of the approach which integrates molecular networking,MolNetEnhancer and Net-work Annotation Propagation(NAP),daphnaltaicanoids A and B(1 and 2)with unprecedented 9-oxa-tetracyclo[6.6.1.0^(2,6).0^(8,13)]pentadecane and tetracyclo[5.3.0.1^(2,5).2^(4,11)]tridecane central frameworks were iso-lated from Daphne altaica Pall.,representing two types of unparalleled meroterpenoid cores.Their struc-tures were elucidated by extensive spectroscopic analysis,nuclear magnetic resonance(NMR)calcula-tions,DP4+analysis and electronic circular dichroism(ECD)calculations.The plausible biosynthetic path-ways for 1 and 2 were postulated.Biologically,2 exerted potent neuroprotective activities which were su-perior to trolox at 12.5 and 25μmol/L.Moreover,1 and 2 exhibited more noticeable acetylcholinesterase inhibitory activities than donepezil.Molecular docking simulations were performed to explore the inter-molecular interaction of compounds 1 and 2 with acetylcholinesterase.The bioactivity evaluation results highlight the prospects of 1 and 2 as a novel category of neurological agents.
基金This work was supported by the Program of National Natural Science Foundation of China(Nos.41906090,81874300,42006092,U1706210,41776141 and 41322037)the Program of Natural Science Foundation of Shandong Province of China(Nos.JQ201510 and ZR2019BD047)+1 种基金Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education,Hainan Normal University(RDZH2021003)the Taishan Scholars Program,China(No.tsqn20161010).
文摘Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides,namely,asperversiamides A–C(1–3)and asperheptatides A–D(4–7)and an unusual pyrroloindoline-containing new cycloheptapeptide,asperpyrroindotide A(8).The structure of 8 was elucidated by comprehensive spectroscopic data analysis,and its absolute configuration was determined by advanced Marfey’s method.The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized.Additionally,a series of new derivatives(10−19)of asperversiamide A(1)was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra.The preliminary structure−activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.
基金The National Natural Science Foundation of China under contract Nos 22264003,42090041 and 42030502the Guangxi Natural Science Fund Project under contract Nos AD17129063,AA17204074 and 2018GXNSFAA281354the Innovation and Entrepreneurship Training Program of College Students from Guangxi University under contract Nos 202210593888 and202210593890。
文摘The chemical diversity of scleractinian corals is closely related to their physiological,ecological,and evolutionary status,and can be influenced by both genetic background and environmental variables.To investigate intraspecific variation in the metabolites of these corals,the metabolomes of four species(Pocillopora meandrina,Seriatopora hystrix,Acropora formosa,and Fungia fungites)from the South China Sea were analyzed using untargeted mass spectrometry-based metabolomics.The results showed that a variety of metabolites,including amino acids,peptides,lipids,and other small molecules,were differentially distributed among the four species,leading to their significant separation in principal component analysis and hierarchical clustering plots.The higher content of storage lipids in branching corals(P.meandrina,S.hystrix,and A.formosa)compared to the solitary coral(F.fungites)may be due to the high densities of zooxanthellae in their tissues.The high content of aromatic amino acids in P.meandrina may help the coral protect against ultraviolet damage and promote growth in shallow seawater,while nitrogen-rich compounds may enable S.hystrix to survive in various challenging environments.The metabolites enriched in F.fungites,including amino acids,dipeptides,phospholipids,and other small molecules,may be related to the composition of the coral's mucus and its life-history,such as its ability to move freely and live solitarily.Studying the chemical diversity of scleractinian corals not only provides insight into their environmental adaptation,but also holds potential for the chemotaxonomy of corals and the discovery of novel bioactive natural products.
基金the Foundation of State Key Laboratory of Component-based Chinese Medicine(Grant No.CBCM2020104).
文摘Objective:Lingzhihuang capsule(LZHC)is a natural product that consists of 10 commonly used medicinal plants,and it is used in traditional Chinese medicine to promote people’s overall health.Previously,LZHC was successfully used as adjuvant therapy for treating patients with cancer.However,the chemical constituents of LZHC and their potential biological functions remain unclear.The aim of this study is to investigate the major bioactive compounds in LZHC and predict their pharmacological targets.Methods:The LZHC constituents were putatively identified by ultra-high performance liquid chromatography coupled with timeof-flight mass spectrometry combined with mass spectrometry-based molecular networking.The targets were predicted using SwissTargetPrediction software,and the associated gene ontology and Kyoto encyclopedia of genes and genomes pathways were analyzed using the Database for Annotation,Visualization,and Integrated Discovery.The mass spectrometry-based molecular network and compound-target-pathway network were constructed using Cytoscape 3.8.0 software.Results:We putatively identified 94 compounds of LZHC by mass spectrometry-based molecular networking,including triterpene(the main structural type)and other clusters(ie,flavonoids and organic acids).Our results suggested that multiple pivotal targets were regulated by LZHC,including tumor necrosis factor,nitric oxide synthase 2,glucocorticoid receptor,estrogen receptor,3-oxo-5-alpha-steroid 4-dehydrogenase 2,prostaglandin e2 receptor ep4 subtype,estrogen receptor beta,phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform,mitogen-activated protein kinase 3,and racalpha serine,which are related to signal transduction,positive regulation of transcription from RNA polymerase II promoters,oxidation-reduction processes,inflammatory responses,and other biological processes.Functional annotation of those targets suggested that several signaling pathways may be regulated by LZHC,such as cancer-related proteoglycans,the PI3K-Aktsignaling
基金This work was supported by the Yangfan Talent Project of Guangdong Province under Grant 201433009the Natural Science Foundation of Guangdong Province under Grant 2018A030307046+7 种基金the Basic Research Project of Shenzhen Science and Technology Innovation Commission under Grant JCYJ20190813105005619the Shenzhen Dapeng New District Industrial Development Fund under Grants KY20180203&PT201901-05the Shenzhen Dapeng New District Scientific and Technological Research and Development Fund under Grant KJYF202001-07the Natural Science Foundation of China under Grant 21807015the Program for Scientific Research Start-Up Funds of Guangdong Ocean University under Grant E15155the Applied S&T Research and Development Major Project of Guangdong Province under Grant 2016B020235001the Scientific Fund of the Zhanjiang Municipal Oceanic and Fishery Bureau under Grant A18018the Project of Enhancing School with Innovation of Guangdong Ocean University(230420022).
文摘Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer's disease.In this paper,the combined bioassay model of acetylcholinesterase(AChE)inhibition,1,1-diphenyl-2-picrylhydrazyl(DPPH)free radical scavenging,and Artemi ci larval lethality was used to evaluate the activity and toxicity of 35 n narine fun gal strains from seas around China.Their bioactive constitue nfs were revealed by thin layer chromatography(TLC)autography,bioactivity coupled LC-MS/MS and Global Natural Products Social Molecular Networking(GNPS).The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound,'tacrine;for which the ratio was 89.8%at 200 pig/ml.Six strains displayed both AChE inhibition(inhibition ratios>20%at 200 pg/ml)and DPPH scavenging activity(scavenging ratios>30%at 200 pg/ml)together with low Artemia larval toxicity(lethal rates<12%).TLC autography showed that the fractioned extracts of four strains contained highly diverse and different bioactive constituents,includi ng strains Talaromyces sp.C2\-\,Aspergillus ter re us C23-3,Trichoderma harzianum DLEN2008005,and Penicillium corylophilum TBG1-17.From the most potent sample F-l 1-1-b(derived from Aspergillus tern us C23-3),five AChE inhibitors and seven antioxida nts were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC-MS/MS,and LC-MS/MS coupled with DPPH incubation.Furthermore,with the aid of GNPS,the AChE inhibitors were plausibly annotated as territrem analogues including territrems A-C/D,arisugacin A and an unknown compound 4,and the seven antioxidants were assigned as butyrolactone I.aspernolide E,a phenolic derivative and possibly unknown compounds 8-10 and 12.
基金supported by the National Natural Science Foundation of China(No.81573550)。
文摘Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines,especially Vernonia amygdalina,a famous nature medicine for the treatment of tonsillitis,diabetes,pneumonia.The current study was designed to combine molecular networking(MN)with diagnostic ions for rapid identification ofΔ^(7,9(11))stigmastane-type saponins which were theα-glucosidase inhibitory active substances in V.amygdalina.First,theα-glucosidase inhibitory activities of fiveΔ^(7,9(11))stigmastane-type steroid saponins that were previously isolated were screened,which indicated that theΔ^(7,9(11))stigmastane-type steroid saponin was one of the active constituents responsible for ameliorating diabetes.Furthermore,a strategy was proposed to identify stigmastane-type steroid saponins and verify the plausibility of derived fragmentation pathways by applying MN,MolNetEnhancer and unsupervised substructure annotation(MS2LDA).Based on this strategy,other sevenΔ^(7,9(11))stigmastane-type steroid saponins were identified from this plant.Our research provide scientific evidence for the antidiabetic potential of the steroid saponin-rich extract of V.amygdalina leaf.
