Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid ...Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,^(13)C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC_(50)values ranging from 0.44 to 4.40μmol·L^(-1).Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(i NOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes,downregulating the expression of inflammation-related proteins,and inhibiting the release of inflammatory cytokines,indicating its potential application in the treatment of inflammatory diseases.展开更多
(±)-Penicithrones A–D(1a/1b–4a/4b),four novel pairs of anthrone–cyclopentenone heterodimers characterized by a distinctive bridged 6/6/6−5 tetracyclic core skeleton,together with three previously identified co...(±)-Penicithrones A–D(1a/1b–4a/4b),four novel pairs of anthrone–cyclopentenone heterodimers characterized by a distinctive bridged 6/6/6−5 tetracyclic core skeleton,together with three previously identified compounds(5–7),were isolated from the crude extract of the mangrove-derived fungus Penicillium sp.,guided by heteronuclear single quantum correlation(HSQC)-based small molecule accurate recognition technology(SMART 2.0)and liquid chromatography-tandem mass spectrometry(LC-MS/MS)-based molecular networking.The structural elucidation of new compounds was accomplished through comprehensive spectroscopic analysis,and their absolute configurations were determined using DP4+^(13)C nuclear magnetic resonance(NMR)calculations and electronic circular dichroism(ECD)calculations.Compounds 1a/1b–4a/4b demonstrated moderate cytotoxicity against three human cancer cell lines HeLa,HCT116 and MCF-7 with half maximal inhibitory concentration(IC50)values ranging from 15.95±1.64 to 28.56±2.59μmol·L–1.展开更多
The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compound...The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compounds 1-5 featured new carbon skeletons in which phloroglucinol derivatives were coupled with lupane-and dammarane-type triterpenoids through different linkage patterns.Their structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and quantum chemical calculations.Biosynthetic pathways for compounds 1-5 were proposed on the basis of the coexisting precursors.Guided by the biogenetic pathways,the biomimetic synthesis of compound 1 was also achieved.Additionally,compounds 2,3,and 5 exhibited potent antiviral activities against herpes simplex virus type-1(HSV-1)infection,and compounds 2 and 5 displayed significant anti-inflammatory activities on RAW264.7 cells.展开更多
Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we pro...Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD’s ACE inhibitory activities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to uncover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.展开更多
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
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 pathway,and the cAMP-signaling pathway.Conclusions:Our findings reveal the chemical constituents of LZHC and provided scientific support for the efficacy of LZHC in terms of immune regulation,anti-aging,and tumor suppression.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
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
[Objectives]This study was conducted to screen lavandulyl flavonoids with anti-inflammatory activity from Sophora flavescens.[Methods]35 compounds were screened from traditional Chinese medicine S.flavescens using the...[Objectives]This study was conducted to screen lavandulyl flavonoids with anti-inflammatory activity from Sophora flavescens.[Methods]35 compounds were screened from traditional Chinese medicine S.flavescens using the nitric oxide(NO)anti-inflammatory activity model.[Results]Five components,8(xanthohumol),13(kurarinol),27(4-methoxysalicylic acid),28(b-resorcic acid)and 30(b-resorcic acid),exhibited significant anti-inflammatory activity,with IC 50 values of 5.99,4.76,6.96,3.41 and 5.22μM,respectively.Especially,8(xanthohumol)and 13(kurarinol)were typical lavandulyl flavonoids in S.flavescens,which were worth further exploration.Furthermore,UPLC-Q-Exactive and GNPS molecular networking technique were used for rapid analysis of lavandulyl flavonoids from S.flavescens.A total of 15 components were identified.[Conclusions]This work lays a theoretical foundation for further separation and analysis of lavandulyl flavonoids with anti-inflammatory activity from S.flavescens.展开更多
Background:Risk substances in cosmetics have long been associated with adverse reactions.However,as risk substances become more concealed and diversified,conventional targeted analysis methods are no longer sufficient...Background:Risk substances in cosmetics have long been associated with adverse reactions.However,as risk substances become more concealed and diversified,conventional targeted analysis methods are no longer sufficient to meet regulatory requirements.Objective:To construct a rapid and effective non-targeted screening method for the identification of risk substances,and to provide a high-throughput method for toxicity assessment.Methods:Molecular networking was utilized for the non-targeted screening of risk substances in facial skincare products,and the toxicity of these risk substances was evaluated through molecular docking and quantitative structure-activity relationship(QSAR)models.Results:Through molecular networking,we identified seven known prohibited ingredients,six of which were confirmed using standard substances.In addition,17 potential risk substances were discovered within molecular clusters containing prohibited ingredients,including antibiotics,antihistamines,and phthalates,etc.Notably,chloramphenicol base and N-desmethyl chlorpheniramine exhibited stronger binding affinity to keratin 5/14 than chloramphenicol and chlorpheniramine through molecular docking,respectively.Additionally,toxicity prediction results indicated that the carcinogenicity of antibiotics presented gender differences in mice and rats,and two chlorpheniramine derivatives also showed carcinogenicity in mice.Moreover,of the 24 compounds,11 showed skin sensitization,while 14 caused skin irritation.Furthermore,half of these compounds demonstrated potential developmental toxicity,and only 4-nitrobenzenethiol was found to be mutagenic.Conclusion:In this study,we developed a visualization strategy for non-targeted screening of risk substances and a high-throughput method for initial toxicity assessment of risk substances.展开更多
The title complex, {[Cu2（4,4＇-bipyridine）2（μ-O2CMe）2（O2CMe）2],H2O}n 1, was synthesized and structurally characterized by X-ray crystallography. It crystallizes in monoclinic, space group C2/c with a = 13.4474...The title complex, {[Cu2（4,4＇-bipyridine）2（μ-O2CMe）2（O2CMe）2],H2O}n 1, was synthesized and structurally characterized by X-ray crystallography. It crystallizes in monoclinic, space group C2/c with a = 13.4474（5）, b = 11.7566（2）, c = 19.5380（6）A, β = 92.930（2）°, V = 3084.84（16） A^3, Z = 4, Cu2C28N409H30, Mr = 693.64, Dc = 1.494 g/cm^3, F（000） = 1424 and μ（MoKα） = 1.436 mm^-1. With the use of 2062 observed reflections （I 〉 2σ（I））, the structure was refined to R = 0.0769 and wR = 0.2154. In complex 1, the dimeric copper acetate units are linked through 4,4’-bipyridine to yield ID molecular ladders. These ladders are connected via O-H…O hydrogen bonds to generate 2D layers, which are further linked through C-H…O hydrogen bonds to give a 3D supramolecular network.展开更多
The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approa...The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approaches have been employed to study the structure, function and dynamics of molecular networks, and begin to reveal important links of various network properties to the functions of the biological systems. In agreement with these functional links, evolutionary selection of a network is apparently based on the function, rather than directly on the structure of the network. Dynamic modularity is one of the prominent features of molecular networks. Taking advantage of such a feature may simplify network-based biological studies through construction of process-specific modular networks and provide functional and mechanistic insights linking genotypic variations to complex traits or diseases, which is likely to be a key approach in the next wave of understanding complex human diseases. With the development of ready-to-use network analysis and modeling tools the networks approaches will be infused into everyday biological research in the near future.展开更多
A novel design of molecular networks for drug delivery application using a PANDA ring resonator is proposed. By using the intense optical vortices generated within the PANDA ring resonator, the required molecules can ...A novel design of molecular networks for drug delivery application using a PANDA ring resonator is proposed. By using the intense optical vortices generated within the PANDA ring resonator, the required molecules can be trapped and moved (transported) dynamically within the wavelength router and bus networks, in which the required drug delivery can perform within the wavelength router before reaching the required destination. PANDA ring is a modified optical add/drop filter. It is a name of Chinese bear, which is used to name the device by the authors. The advantage of the proposed system is that the drug delivery networks can perform within the tiny system (thin film device), where the large molecular drug networks such as ring, star and bus networks are also proposed, in which the applications such as Alzheimers’ and Parkinson diagnosis, blood circulation networks and in situ surgery operation are discussed.展开更多
MS/MS-based molecular networking is an effective strategy to rapidly dereplicate known compounds and to guide the discovery process for new and novel natural products.In the present study,the chemical diversity of ind...MS/MS-based molecular networking is an effective strategy to rapidly dereplicate known compounds and to guide the discovery process for new and novel natural products.In the present study,the chemical diversity of indole diterpenoids from the marine-derived fungus Penicillium sp.N4-3 was investigated using molecular networking techniques.Guided by this information,targeted isolation resulted in two new indole diterpenoids shearinines R and S(1,2)and an oxidative artifact shearinine T(3),together with the verification of two known analogs(4,5).Furthermore,five indole diterpenoids(6−10),including three putatively new ones,shearinines U−W(6,9,10),were predicted from the molecular ion cluster by the combination of GNPS molecular networking and manual analysis of MS/MS fragmentation clusters.Shearinines T(3)and W(10)are characterized by an oxidative cleavage of the C-2–C-18 double bond.Feature fragment ions of these shearinines revealed two type of dominant ions related to the indole moiety and the breaking of C-9 side chain or Ring I.Compound 1 showed antibacterial activities against a panel of pathogenic bacteria with IC_(50) values ranging from 6.34 to 47.96μg/mL and inhibited the growth of the human hepatic(HepG2)and gastric(SGC-7901)cancer cells lines with IC_(50) values of 6.27 and 19.16μg/mL,respectively.展开更多
To the editor:The comprehensive exploration of natural products and metabolites is essential for unraveling the complexities of natural drug therapies.Inadequate tracking and separation methods result in increased res...To the editor:The comprehensive exploration of natural products and metabolites is essential for unraveling the complexities of natural drug therapies.Inadequate tracking and separation methods result in increased research costs and reduced scientific output,significantly hindering the healthy advancement of related research fields.Emerging molecular networking(MN)technologies help minimize the redundant discovery of known natural products or metabolites.展开更多
Background:Drug resistance is increasing in gastrointestinal parasitosis;it is therefore essential to identify new anthelmintic molecules.Objective:The study aims to evaluate the anthelmintic activity of extracts and ...Background:Drug resistance is increasing in gastrointestinal parasitosis;it is therefore essential to identify new anthelmintic molecules.Objective:The study aims to evaluate the anthelmintic activity of extracts and fractions of leaves of Saba sene-galensis(A.DC.)Pichon(Apocynaceae)against L_(3)larvae of Caenorhabditis elegans,a free-living helminth model and to highlight potential anthelmintic molecules by dereplication strategy of molecular networking.Methods:The methanolic extract,ethanolic extract and aqueous extract of the plant’s leaves were carried out,followed by flash chromatography on silica gel for by fractionation,HPLC-MS/MS analysis.The tandem mass data were used for generation of molecular network.The anthelmintic effects of aqueous and hydro-ethanolic fractions of leaves of S.senegalensis on Caenorhabditis elegans worm viability were carried out by using both 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide(MTT)assay and microscope motility observation.Results:Among the aqueous fractions,the aqueous decoction showed an EC_(50)at 0.24 mg/ml and a viability rate of 7.5%at 0.9 mg/ml.In hydro-ethanolic extracts,hydro-ethanolic macerate residual(Fe-3)exhibited a significant effect with an EC_(50)at 0.29 mg/ml and 12.5%of viability at 0.9 mg/ml.HPLC-ESI-MS/MS analysis allowed the identification of twelve compounds.Conclusions:Using the MTT-formazan assay,extracts of S.senegalensis exhibit a moderate anthelmintic effect on C.elegans worms linked to natural antiparasitic molecules.展开更多
Sarcaglarols A-D(1-4),two pairs of lindenane-monoterpene heterodimers fused by a 1,2-dioxane moiety,were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy....Sarcaglarols A-D(1-4),two pairs of lindenane-monoterpene heterodimers fused by a 1,2-dioxane moiety,were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy.Their planar structures,absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS,NMR spectroscopic data,ECD spectrum,and the X-ray diffraction study of isopropylidene derivatives.An intermolecular[2+2+2]cycloaddition may play a key role in the biosynthesis pathway of the 1,2-dioxane moiety fused lindenane-monoterpene heterodimer skeleton,which can be recognized as the biogenetic precursors of our previous reported lindenane-normonoterpene conjugates.In addition,compounds 1,3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid-exposed L02 cells.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 building blocks-based molecular network(BBMN)strategy was applied to the phytochemical investigation of Cleistocalyx operculatus,leading to the targeted isolation of eighteen novel cinnamoylphloroglucinol-terpene ...The building blocks-based molecular network(BBMN)strategy was applied to the phytochemical investigation of Cleistocalyx operculatus,leading to the targeted isolation of eighteen novel cinnamoylphloroglucinol-terpene adducts(CPTAs)with diverse skeleton types(cleistoperones A-R,1-18).Their structures including absolute configurations were determined by extensive spectroscopic methods,quantum chemical calculations,and single-crystal X-ray crystallographic experiments.Cleistoperone A(1),consisting of a cinnamoylphloroglucinol motif and two linear monoterpene moieties,represents an unprecedented macrocyclic CPTA,whose densely functionalized tricyclo[15.3.1.0^(3,8)]heneicosane bridge ring skeleton contains an enolizableβ,β′-triketone system and two different kinds of stereogenic elements(including five point and three planar chiralities).Cleistoperones B and C(2 and 3)are two new skeletal CPTAs with an unusual coupling pattern between the(nor)monoterpene moiety and the cinnamoyl chain of the cinnamoylphloroglucinol unit.Cleistoperone D(4)possesses an unprecedented cage-like 6/6/6/4/6-fused heteropentacyclic scaffold.The plausible biosynthetic pathways for 1-18 were also proposed.Notably,compounds 1,4,7,8,and 18 exhibited significant antiviral activity against respiratory syncytial virus(RSV).The most potent one,cleistoperone A(1)with IC_(50) value of 1.71±0.61μmol/L,could effectively inhibit virus replication via affecting the Akt/mTOR/p70S6K signaling pathway.展开更多
Identifying biomarkers for accurate diagnosis and prognosis of diseases is important for the prevention of disease development. The molecular networks that describe the functional relationships among molecules provide...Identifying biomarkers for accurate diagnosis and prognosis of diseases is important for the prevention of disease development. The molecular networks that describe the functional relationships among molecules provide a global view of the complex biological systems. With the molecular networks, the molecular mechanisms underlying diseases can be unveiled, which helps identify biomarkers in a systematic way. Results： In this survey, we report the recent progress on identifying biomarkers based on the topology of molecular networks, and we categorize those biomarkers into three groups, including node biomarkers, edge biomarkers and network biomarkers. These distinct types of biomarkers can be detected under different conditions depending on the data available. Conclusions： The biomarkers identified based on molecular networks can provide more accurate diagnosis and prognosis. The pros and cons of different types of hiomarkers as well as future directions to improve the methods for identifying biomarkers are also discussed.展开更多
基金funded by the National Key Research and Development Program of China(No.2022YFC2804101)the Guangdong Provincial Key R&D Program(No.2023B1111050011)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515010432)the Guangzhou Basic and Applied Basic Research Foundation(No.202201010305)the High-Level Talents Special Program of Zhejiang(No.2022R52036)。
文摘Guided by molecular networking,nine novel curvularin derivatives(1-9)and 16 known analogs(10-25)were isolated from the hydrothermal vent sediment fungus Penicillium sp.HL-50.Notably,compounds 5-7 represented a hybrid of curvularin and purine.The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance(NMR)spectroscopy,X-ray diffraction,electronic circular dichroism(ECD)calculations,^(13)C NMR calculation,modified Mosher's method,and chemical derivatization.Investigation of anti-inflammatory activities revealed that compounds 7-9,11,12,14,15,and 18 exhibited significant suppressive effects against lipopolysaccharide(LPS)-induced nitric oxide(NO)production in murine macrophage RAW264.7 cells,with IC_(50)values ranging from 0.44 to 4.40μmol·L^(-1).Furthermore,these bioactive compounds were found to suppress the expression of inflammation-related proteins,including inducible NO synthase(i NOS),cyclooxygenase-2(COX-2),NLR family pyrin domain-containing protein 3(NLRP3),and nuclear factor kappa-B(NF-κB).Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes,downregulating the expression of inflammation-related proteins,and inhibiting the release of inflammatory cytokines,indicating its potential application in the treatment of inflammatory diseases.
基金supported by the National Key Research and Development Program of China(No.2022YFC2303100)the National Natural Science Foundation of China(Nos.32022002 and 21977113).
文摘(±)-Penicithrones A–D(1a/1b–4a/4b),four novel pairs of anthrone–cyclopentenone heterodimers characterized by a distinctive bridged 6/6/6−5 tetracyclic core skeleton,together with three previously identified compounds(5–7),were isolated from the crude extract of the mangrove-derived fungus Penicillium sp.,guided by heteronuclear single quantum correlation(HSQC)-based small molecule accurate recognition technology(SMART 2.0)and liquid chromatography-tandem mass spectrometry(LC-MS/MS)-based molecular networking.The structural elucidation of new compounds was accomplished through comprehensive spectroscopic analysis,and their absolute configurations were determined using DP4+^(13)C nuclear magnetic resonance(NMR)calculations and electronic circular dichroism(ECD)calculations.Compounds 1a/1b–4a/4b demonstrated moderate cytotoxicity against three human cancer cell lines HeLa,HCT116 and MCF-7 with half maximal inhibitory concentration(IC50)values ranging from 15.95±1.64 to 28.56±2.59μmol·L–1.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515120066 and 2022A1515010010)the National Natural Science Foundation of China[Nos.82293681(82293680)and 82273822]+3 种基金the Science and Technology Key Project of Guangdong Province(No.2020B1111110004)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)the Fundamental Research Funds for the Central Universitiesthe support of K.C.Wong Education Foundation。
文摘The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compounds 1-5 featured new carbon skeletons in which phloroglucinol derivatives were coupled with lupane-and dammarane-type triterpenoids through different linkage patterns.Their structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and quantum chemical calculations.Biosynthetic pathways for compounds 1-5 were proposed on the basis of the coexisting precursors.Guided by the biogenetic pathways,the biomimetic synthesis of compound 1 was also achieved.Additionally,compounds 2,3,and 5 exhibited potent antiviral activities against herpes simplex virus type-1(HSV-1)infection,and compounds 2 and 5 displayed significant anti-inflammatory activities on RAW264.7 cells.
基金financially supported by the National Key R&D Program of China(Grant No.:2018YFC1704502)the National Natural Science Foundation of China(Grant No.:81603268)the National Natural Science Foundation of China(Grant No.:81822047)
文摘Natural products are great treasure troves for the discovery of bioactive components.Current bioassay guided fractionation for identification of bioactive components is time-and workload-consuming.In this study,we proposed a robust and convenient strategy for deciphering the bioactive profile of natural products by mass spectral molecular networking combined with rapid bioassay.As a proof-of-concept,the strategy was applied to identify angiotensin converting enzyme(ACE)inhibitors of Fangjihuangqi decoction(FJHQD),a traditional medicine clinically used for the treatment of heart failure.The chemical profile of FJHQD was comprehensively revealed with the assistance of tandem mass spectral molecular networking,and a total of 165 compounds were identified.With characterized constituents,potential clinical applications of FJHQD were predicted by Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine,and a range of cardiovascular related diseases were significantly enriched.ACE inhibitory activities of FJHQD and its constituents were then investigated with an aggregation-induced emission based fluorescent probe.FJHQD exhibited excellent ACE inhibitory effects,and a bioactive molecular network was established to elucidate the ACE inhibitory profile of constituents in FJHQD.This bioactive molecular network provided a panoramic view of FJHQD’s ACE inhibitory activities,which demonstrated that flavones from Astragali Radix and Glycyrrhizae Radix et Rhizoma,saponins from Astragali Radix,and sesquiterpenoids from Atractylodis Macrocephalae Rhizoma were principal components responsible for this effect of FJHQD.Among them,four novel ACE inhibitors were the first to be reported.Our study indicated that the proposed strategy offers a useful approach to uncover the bioactive profile of traditional medicines and provides a pragmatic workflow for exploring bioactive components.
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 pathway,and the cAMP-signaling pathway.Conclusions:Our findings reveal the chemical constituents of LZHC and provided scientific support for the efficacy of LZHC in terms of immune regulation,anti-aging,and tumor suppression.
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.
基金Supported by Guizhou Provincial Science and Technology(ZK(2022)-362,ZK(2024)-047,[2023]ZK01)The Innovation and Entrepreneurship Training Program for Undergraduates from China[202210660131,202310660082]+2 种基金Science Foundation of Guizhou Education Technology(2022-064)University Engineering Research Center for the Prevention and Treatment of Chronic Diseases by Authentic Medicinal Materials in Guizhou Province([2023]035)Science and Technology Research Project of Guizhou Administration of Traditional Chinese Medicine(QZYY-2024-134).
文摘[Objectives]This study was conducted to screen lavandulyl flavonoids with anti-inflammatory activity from Sophora flavescens.[Methods]35 compounds were screened from traditional Chinese medicine S.flavescens using the nitric oxide(NO)anti-inflammatory activity model.[Results]Five components,8(xanthohumol),13(kurarinol),27(4-methoxysalicylic acid),28(b-resorcic acid)and 30(b-resorcic acid),exhibited significant anti-inflammatory activity,with IC 50 values of 5.99,4.76,6.96,3.41 and 5.22μM,respectively.Especially,8(xanthohumol)and 13(kurarinol)were typical lavandulyl flavonoids in S.flavescens,which were worth further exploration.Furthermore,UPLC-Q-Exactive and GNPS molecular networking technique were used for rapid analysis of lavandulyl flavonoids from S.flavescens.A total of 15 components were identified.[Conclusions]This work lays a theoretical foundation for further separation and analysis of lavandulyl flavonoids with anti-inflammatory activity from S.flavescens.
基金supported by the Scientific and technological innovation project of Guangdong Provincial Drug Administration(ZA20230069,2024ZDZ04)the Science and Technology Plan Project of Guangdong Provincial(2023A1111120025).
文摘Background:Risk substances in cosmetics have long been associated with adverse reactions.However,as risk substances become more concealed and diversified,conventional targeted analysis methods are no longer sufficient to meet regulatory requirements.Objective:To construct a rapid and effective non-targeted screening method for the identification of risk substances,and to provide a high-throughput method for toxicity assessment.Methods:Molecular networking was utilized for the non-targeted screening of risk substances in facial skincare products,and the toxicity of these risk substances was evaluated through molecular docking and quantitative structure-activity relationship(QSAR)models.Results:Through molecular networking,we identified seven known prohibited ingredients,six of which were confirmed using standard substances.In addition,17 potential risk substances were discovered within molecular clusters containing prohibited ingredients,including antibiotics,antihistamines,and phthalates,etc.Notably,chloramphenicol base and N-desmethyl chlorpheniramine exhibited stronger binding affinity to keratin 5/14 than chloramphenicol and chlorpheniramine through molecular docking,respectively.Additionally,toxicity prediction results indicated that the carcinogenicity of antibiotics presented gender differences in mice and rats,and two chlorpheniramine derivatives also showed carcinogenicity in mice.Moreover,of the 24 compounds,11 showed skin sensitization,while 14 caused skin irritation.Furthermore,half of these compounds demonstrated potential developmental toxicity,and only 4-nitrobenzenethiol was found to be mutagenic.Conclusion:In this study,we developed a visualization strategy for non-targeted screening of risk substances and a high-throughput method for initial toxicity assessment of risk substances.
基金This work was supported by the Science Foundation of Fujian Provincial Key Laboratory of Polymer Materials
文摘The title complex, {[Cu2（4,4＇-bipyridine）2（μ-O2CMe）2（O2CMe）2],H2O}n 1, was synthesized and structurally characterized by X-ray crystallography. It crystallizes in monoclinic, space group C2/c with a = 13.4474（5）, b = 11.7566（2）, c = 19.5380（6）A, β = 92.930（2）°, V = 3084.84（16） A^3, Z = 4, Cu2C28N409H30, Mr = 693.64, Dc = 1.494 g/cm^3, F（000） = 1424 and μ（MoKα） = 1.436 mm^-1. With the use of 2062 observed reflections （I 〉 2σ（I））, the structure was refined to R = 0.0769 and wR = 0.2154. In complex 1, the dimeric copper acetate units are linked through 4,4’-bipyridine to yield ID molecular ladders. These ladders are connected via O-H…O hydrogen bonds to generate 2D layers, which are further linked through C-H…O hydrogen bonds to give a 3D supramolecular network.
文摘The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approaches have been employed to study the structure, function and dynamics of molecular networks, and begin to reveal important links of various network properties to the functions of the biological systems. In agreement with these functional links, evolutionary selection of a network is apparently based on the function, rather than directly on the structure of the network. Dynamic modularity is one of the prominent features of molecular networks. Taking advantage of such a feature may simplify network-based biological studies through construction of process-specific modular networks and provide functional and mechanistic insights linking genotypic variations to complex traits or diseases, which is likely to be a key approach in the next wave of understanding complex human diseases. With the development of ready-to-use network analysis and modeling tools the networks approaches will be infused into everyday biological research in the near future.
文摘A novel design of molecular networks for drug delivery application using a PANDA ring resonator is proposed. By using the intense optical vortices generated within the PANDA ring resonator, the required molecules can be trapped and moved (transported) dynamically within the wavelength router and bus networks, in which the required drug delivery can perform within the wavelength router before reaching the required destination. PANDA ring is a modified optical add/drop filter. It is a name of Chinese bear, which is used to name the device by the authors. The advantage of the proposed system is that the drug delivery networks can perform within the tiny system (thin film device), where the large molecular drug networks such as ring, star and bus networks are also proposed, in which the applications such as Alzheimers’ and Parkinson diagnosis, blood circulation networks and in situ surgery operation are discussed.
基金supported by National Natu-ral Science Foundation of China(Nos.4183053581703411)+3 种基金Key Research and Development Project(Social Develop-ment)of Yangzhou(No.YZ2023068)Shandong Provincial Nat-ural Science Foundation,China(Major Basic Research Projects)(ZR2019ZD18)the Program of Open Studio for Druggability Research of Marine Natural Products,National Laboratory for Marine Science and Technology(Qingdao,China)Directed by Kai-Xian Chen and Yue-Wei GuoTaishan Scholars Program,China.
文摘MS/MS-based molecular networking is an effective strategy to rapidly dereplicate known compounds and to guide the discovery process for new and novel natural products.In the present study,the chemical diversity of indole diterpenoids from the marine-derived fungus Penicillium sp.N4-3 was investigated using molecular networking techniques.Guided by this information,targeted isolation resulted in two new indole diterpenoids shearinines R and S(1,2)and an oxidative artifact shearinine T(3),together with the verification of two known analogs(4,5).Furthermore,five indole diterpenoids(6−10),including three putatively new ones,shearinines U−W(6,9,10),were predicted from the molecular ion cluster by the combination of GNPS molecular networking and manual analysis of MS/MS fragmentation clusters.Shearinines T(3)and W(10)are characterized by an oxidative cleavage of the C-2–C-18 double bond.Feature fragment ions of these shearinines revealed two type of dominant ions related to the indole moiety and the breaking of C-9 side chain or Ring I.Compound 1 showed antibacterial activities against a panel of pathogenic bacteria with IC_(50) values ranging from 6.34 to 47.96μg/mL and inhibited the growth of the human hepatic(HepG2)and gastric(SGC-7901)cancer cells lines with IC_(50) values of 6.27 and 19.16μg/mL,respectively.
基金supported by grants from the National Natural Science Foundation of China(82430116 and 82204607)The special fund of Central committee high level Chinese medicine hospital(CZ015-DZMG-LJRC-0014,DZMG-LJRC0013,China)Young Elite Scientists Sponsorship Program by CACM(2023-QNRC2-B18,China).
文摘To the editor:The comprehensive exploration of natural products and metabolites is essential for unraveling the complexities of natural drug therapies.Inadequate tracking and separation methods result in increased research costs and reduced scientific output,significantly hindering the healthy advancement of related research fields.Emerging molecular networking(MN)technologies help minimize the redundant discovery of known natural products or metabolites.
基金financial support from Campus France(895739H)through the French Embassy in Burkina Faso.
文摘Background:Drug resistance is increasing in gastrointestinal parasitosis;it is therefore essential to identify new anthelmintic molecules.Objective:The study aims to evaluate the anthelmintic activity of extracts and fractions of leaves of Saba sene-galensis(A.DC.)Pichon(Apocynaceae)against L_(3)larvae of Caenorhabditis elegans,a free-living helminth model and to highlight potential anthelmintic molecules by dereplication strategy of molecular networking.Methods:The methanolic extract,ethanolic extract and aqueous extract of the plant’s leaves were carried out,followed by flash chromatography on silica gel for by fractionation,HPLC-MS/MS analysis.The tandem mass data were used for generation of molecular network.The anthelmintic effects of aqueous and hydro-ethanolic fractions of leaves of S.senegalensis on Caenorhabditis elegans worm viability were carried out by using both 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide(MTT)assay and microscope motility observation.Results:Among the aqueous fractions,the aqueous decoction showed an EC_(50)at 0.24 mg/ml and a viability rate of 7.5%at 0.9 mg/ml.In hydro-ethanolic extracts,hydro-ethanolic macerate residual(Fe-3)exhibited a significant effect with an EC_(50)at 0.29 mg/ml and 12.5%of viability at 0.9 mg/ml.HPLC-ESI-MS/MS analysis allowed the identification of twelve compounds.Conclusions:Using the MTT-formazan assay,extracts of S.senegalensis exhibit a moderate anthelmintic effect on C.elegans worms linked to natural antiparasitic molecules.
基金Financial support for this study is from the"Double First-Class"University project(CPU2018GY08,China)the 111 Project from Ministry of Education of China and the State Administration of Foreign Export Affairs of China(B18056)the National New Drug Innovation Major Project(2018ZX09711-001-007).
文摘Sarcaglarols A-D(1-4),two pairs of lindenane-monoterpene heterodimers fused by a 1,2-dioxane moiety,were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy.Their planar structures,absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS,NMR spectroscopic data,ECD spectrum,and the X-ray diffraction study of isopropylidene derivatives.An intermolecular[2+2+2]cycloaddition may play a key role in the biosynthesis pathway of the 1,2-dioxane moiety fused lindenane-monoterpene heterodimer skeleton,which can be recognized as the biogenetic precursors of our previous reported lindenane-normonoterpene conjugates.In addition,compounds 1,3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid-exposed L02 cells.
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supported by the National Key R&D Program of China(No.2023YFC3503902,China)the National Natural Science Foundation of China(Nos.82293681(82293680)+6 种基金82321004,82204234,and 82273822,China)the Guangdong Basic and Applied Basic Research Foundation(Nos.2022B1515120015 and 2021A1515111021,China)the Guangdong Major Project of Basic and Applied Basic Research(No.2023B0303000026,China)the Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine(No.2023LSYS002,China)the Guangzhou Key Laboratory of Traditional Chinese Medicine&Disease Susceptibility(No.2024A03J090,China)the Science and Technology Projects in Guangzhou(No.202102070001,China)supported by the high-performance computing platform of Jinan University.
文摘The building blocks-based molecular network(BBMN)strategy was applied to the phytochemical investigation of Cleistocalyx operculatus,leading to the targeted isolation of eighteen novel cinnamoylphloroglucinol-terpene adducts(CPTAs)with diverse skeleton types(cleistoperones A-R,1-18).Their structures including absolute configurations were determined by extensive spectroscopic methods,quantum chemical calculations,and single-crystal X-ray crystallographic experiments.Cleistoperone A(1),consisting of a cinnamoylphloroglucinol motif and two linear monoterpene moieties,represents an unprecedented macrocyclic CPTA,whose densely functionalized tricyclo[15.3.1.0^(3,8)]heneicosane bridge ring skeleton contains an enolizableβ,β′-triketone system and two different kinds of stereogenic elements(including five point and three planar chiralities).Cleistoperones B and C(2 and 3)are two new skeletal CPTAs with an unusual coupling pattern between the(nor)monoterpene moiety and the cinnamoyl chain of the cinnamoylphloroglucinol unit.Cleistoperone D(4)possesses an unprecedented cage-like 6/6/6/4/6-fused heteropentacyclic scaffold.The plausible biosynthetic pathways for 1-18 were also proposed.Notably,compounds 1,4,7,8,and 18 exhibited significant antiviral activity against respiratory syncytial virus(RSV).The most potent one,cleistoperone A(1)with IC_(50) value of 1.71±0.61μmol/L,could effectively inhibit virus replication via affecting the Akt/mTOR/p70S6K signaling pathway.
基金This work was partly supported by the National Nature Science Foundation of China （Nos. 91530321, 61390513, 61602347 and 61572363）, and the Fundamental Research Funds for the Central Universities.
文摘Identifying biomarkers for accurate diagnosis and prognosis of diseases is important for the prevention of disease development. The molecular networks that describe the functional relationships among molecules provide a global view of the complex biological systems. With the molecular networks, the molecular mechanisms underlying diseases can be unveiled, which helps identify biomarkers in a systematic way. Results： In this survey, we report the recent progress on identifying biomarkers based on the topology of molecular networks, and we categorize those biomarkers into three groups, including node biomarkers, edge biomarkers and network biomarkers. These distinct types of biomarkers can be detected under different conditions depending on the data available. Conclusions： The biomarkers identified based on molecular networks can provide more accurate diagnosis and prognosis. The pros and cons of different types of hiomarkers as well as future directions to improve the methods for identifying biomarkers are also discussed.
