Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products socia...Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products social molecular networking(OSMAC-GNPS)strategy,a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp.EGF 15-0-3.Structurally,sterpiperazines A(1)and B(2)represent the first steroid-based indole alkaloids with unprecedented backbones.Biologically,compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1(Tdp1)inhibitor with a unique mechanism distinct from the reported modulators,and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.展开更多
Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,whic...Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,which utilize vinylene carbonate as a new C2 synthon.This protocol is expected to provide a facile and useful access to various indole derivatives.展开更多
Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]iso...Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.展开更多
multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from e...multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from enamine ketone,aromatic ketone aldehyde hydrate,and carboxylic acid,and selectively synthesized 7-ester indoles and bis-indoles by changing the substituted enamine ketone substrate.This method had the characteristics of high regional selectivity,short reaction time,and green environmental protection.展开更多
Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the con...Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.展开更多
Cycloheptatriene is a privileged structural motif present in many bioactive compounds,pharmaceutical agents and natural products,especially in a large number of core structures of sesquiterpenoids.Herein,a mild and ef...Cycloheptatriene is a privileged structural motif present in many bioactive compounds,pharmaceutical agents and natural products,especially in a large number of core structures of sesquiterpenoids.Herein,a mild and efficient synthetic approach was reported for access of a series of C2 or C3-(cycloheptatrienyl)-substituted indoles.A wide range of functional groups can be well tolerated in this transformation,especially including hydroxyl,halo,carboxylic acid and its derivative groups.Based on these results,a rational mechanism via electrophilic substitution of indoles with tropylium tetrafluoroborate is proposed.展开更多
Zeng N,Ye G,Zheng M,Liu G,Zhang S,Ma S,Xia Z,Zhou Y,Wang S,Xia Q.Discovery and validation of indole nitroolefins as novel covalent GPX4 inhibitors for inducing ferroptosis in urological cancers.Chin J Cancer Res 2025;...Zeng N,Ye G,Zheng M,Liu G,Zhang S,Ma S,Xia Z,Zhou Y,Wang S,Xia Q.Discovery and validation of indole nitroolefins as novel covalent GPX4 inhibitors for inducing ferroptosis in urological cancers.Chin J Cancer Res 2025;37(3):404-416.doi:10.21147/j.issn.1000-9604.2025.03.09.展开更多
Recently,more and more bacteria have been reported to become tolerant to antibiotics.In this study,one tnaA gene involved in indole production,and the effect of exogenous indole on the formation of persister cells spe...Recently,more and more bacteria have been reported to become tolerant to antibiotics.In this study,one tnaA gene involved in indole production,and the effect of exogenous indole on the formation of persister cells specific to tetracycline in Vibrio splendidus were characterized.The tnaA Vs gene was first cloned and conditionally expressed in Escherichia coli Rosetta(DE3).To investigate the regulatory effect of TnaA Vs,the tnaA deletion strain AJ01/ΔtnaA was constructed by in-frame deletion.The undetected extracellular indole in the AJ01/ΔtnaA indicated that TnaA was the solo enzyme to produce indole in V.splendidus.The drop plate method showed that AJ01/ΔtnaA was more tolerant to the higher concentration of tetracycline than that of AJ01,being 340-fold higher in the proportion of survived cells when cell density OD 600≈0.65.Moreover,the synergistic effects of indole and tetracycline on killing of V.splendidus were determined.Results show that addition of 2-mmol/L indole increased the susceptibility of both AJ01 and AJ01/ΔtnaA to 10×minimum inhibitory concentration tetracycline.To explore the genes and pathways regulated by TnaA Vs,the transcriptomic analysis between AJ01 and AJ01/ΔtnaA was performed.Result shows that TCA cycle,arginine biosynthesis,quorum sensing and microbial metabolism in diverse environments were downregulated,while the ribosome pathways,the protein metabolic process,peptide biosynthetic and metabolic process were upregulated in the AJ01/ΔtnaA.This study shows that indole could enhance the bactericidal effect of tetracycline on V.splendidus by decreased ribosome level probably but increased ATP level.展开更多
Skeletal editing has emerged as a powerful tool in organic chemistry,enabling the simplification of synthetic routes to complex molecules[1].Indoles,electron-rich nitrogen-containing building blocks,represent privileg...Skeletal editing has emerged as a powerful tool in organic chemistry,enabling the simplification of synthetic routes to complex molecules[1].Indoles,electron-rich nitrogen-containing building blocks,represent privileged scaffolds prevalent in pharmaceuticals,natural products,and bioactive compounds.The application of skeletal editing strategies to modify such structures is highly valuable and in growing demand.Leveraging the electronrich nature of indoles at C2 and C3,single-carbon atom insertion using cationic carbyne equivalents offers an efficient approach for indole ring expansion to quinoline(Scheme 1a).However,existing methods predominantly rely on halocarbene precursors,which restricts the functional groups of ring-expanded products to halogen[2],alkyl,aryl,heteroaryl and ester moieties[3].This limitation hinders their utility in late-stage skeletal modifications of complex targets.展开更多
BACKGROUND Indolent T-cell lymphoma of the gastrointestinal tract(iTCL-GI)is a rare mature T-cell lymphoma that has been formally recognized as a distinct entity in the 5th Edition World Health Organization Classifica...BACKGROUND Indolent T-cell lymphoma of the gastrointestinal tract(iTCL-GI)is a rare mature T-cell lymphoma that has been formally recognized as a distinct entity in the 5th Edition World Health Organization Classification of Tumours of Haematolymphoid Tumours.However,the coexistence of iTCL-GI with epithelial malignancies is rare in clinical practice.This study reports a case of iTCL-GI with gastric signet-ring cell carcinoma(SRCC).We aim to increase diagnostic awareness among clinicians and pathologists regarding multiple primary tumors.CASE SUMMARY A 65-year-old female presented with a 5-month history of lower abdominal pain,bloating,and vomiting.An abdominal computed tomography scan revealed irregular thickening of the gastric wall.Endoscopy revealed diffuse mucosal edema and rigid mucosa along the lesser curvature of the gastric body.There was a 1.5 cm mucosal protrusion on the greater curvature.Biopsy revealed that the lamina propria was expanded by a dense,nondestructive infiltrate of small lymphocytes in the greater curvature,which were characterized by a CD3+/CD8+/TIA-1+immunophenotype with a low Ki-67 index.Clonal T-cell receptor rearrangement was detected,but the Epstein-Barr virus encoded RNA's was negative.Lesions on the lesser curvature of the gastric body were confirmed to be SRCCs.After three months of follow-up,the patient completed four cycles of chemotherapy targeting the SRCC.While her abdominal pain improved,she experienced a weight loss of 5 kg.CONCLUSION Clinicians and pathologists must integrate assessment of these rare cases to prevent misdiagnosis and guide clinical practice.展开更多
BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically e...BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically exhibits a benign or slowly progressive clinical course,with disease localized to the gastrointestinal tract.Here,we present what we believe to be the first reported case of iNKLPD associated with protein-losing enteropathy(PLE),characterized by a poor response to chemotherapy and rapid clinical deterioration,culminating in death within a few months.CASE SUMMARY We report the case of a 64-year-old man who presented with bilateral lower-extremity edema and fatigue.Laboratory tests revealed marked hypoalbuminemia,while other liver function parameters remained within normal limits.Renal and cardiac function assessments were unremarkable.Histopathological examination of endoscopic biopsies confirmed a diagnosis of iNKLPD of the gastrointestinal tract.The patient was treated with oral prednisone and cyclosporine,which led to temporary improvement in both symptoms and serum albumin levels.However,disease relapse occurred during corticosteroid tapering,accompanied by worsening hypoalbu-minemia and refractory diarrhea.The patient died eight months after diagnosis,likely due to disease progression or severe treatment-related complications.CONCLUSION iNKLPD generally exhibits an indolent course;nonetheless,the prognosis may be poor if secondary PLE is involved.展开更多
Nanosized fibrous cerium（IV） hydrogen phosphate membrane, Ce（HPO4）2·2.9H20 （nCePf）, was prepared and characterized by chemical, XRD （X-ray diffraction）, TGA （thermogravimetric analysis）, SEM （scanning ...Nanosized fibrous cerium（IV） hydrogen phosphate membrane, Ce（HPO4）2·2.9H20 （nCePf）, was prepared and characterized by chemical, XRD （X-ray diffraction）, TGA （thermogravimetric analysis）, SEM （scanning electron microscopy） and TEM （transmission electron microscopy）. Novel supported nanofibrous Ce（IV） phosphate/polyiondole nanocomposite membranes were prepared via in-situ chemical oxidation of the monomer that was promoted by the reduction of Ce（IV） ions present in the inorganic matrix. The presence of Ce（IV） ions allows redox reactions necessary to oxidative polymerization to occur. The resultant material was characterized by TGA, elemental （C, H, N） analysis and FT-IR （Fourier transform spectroscopy）. SEM images of the resulting nanocomposite reveals a uniform distribution of the polymer on the inorganic matrix. Amount of polyindole polymer present in the composite is found to be - 7.0%.展开更多
From the aerial parts ofNauclea officinalis （Pierre ex Pitard） Merr. et Churl, one new indole alkaloid paratunamide E （1） has been isolated together with six known indole alkaloids, paratunamide A （2）, nauclealo...From the aerial parts ofNauclea officinalis （Pierre ex Pitard） Merr. et Churl, one new indole alkaloid paratunamide E （1） has been isolated together with six known indole alkaloids, paratunamide A （2）, nauclealotide C （3）, nauclealotide A （4）, vincosamide （5）, strictosamide （6） and naucleamide F （7）. Naucleamide F （7） was isolated from Nauclea officinalis for the first time. All of the seven compounds above were elucidated by spectroscopic methods including 1 D and 2 D NMR soectroscoDic analyses.展开更多
Jasmonic acid （JA） is a fatty acid-derived signaling molecule that regulates a broad range of plant defense responses against herbivores and some microbial pathogens. Molecular genetic studies have established that ...Jasmonic acid （JA） is a fatty acid-derived signaling molecule that regulates a broad range of plant defense responses against herbivores and some microbial pathogens. Molecular genetic studies have established that JA also performs a critical role in several aspects of plant development. Here, we describe the characterization of the Arabidopsis mutantjasmonic acid-hypersensitivel-1 （jah1-1）, which is defective in several aspects of JA responses. Although the mutant exhibits increased sensitivity to JA in root growth inhibition, it shows decreased expression of JA-inducible defense genes and reduced resistance to the necrotrophic fungus Botrytis cinerea. Gene cloning studies indicate that these defects are caused by a mutation in the cytochrome P450 protein CYP82C2. We provide evidence showing that the compromised resistance of thejah1-1 mutant to B. cinerea is accompanied by decreased expression of JA-induced defense genes and reduced accumulation of JA-induced indole glucosinolates （IGs）. Conversely, the enhanced resistance to B. cinerea in CYP82C2-overexpressing plants is accompanied by increased expression of JA-induced defense genes and elevated levels of JA-induced IGs. We demonstrate that CYP82C2 affects JA-induced accumulation of the IG biosynthetic precursor tryptophan （Trp）, but not the JA-induced IAA or pathogen-induced camalexin. Together, our results support a hypothesis that CYP82C2 may act in the metabolism of Trp-derived secondary metabolites under conditions in which JA levels are elevated. Thejah1-1 mutant should thus be important in future studies toward understanding the mechanisms underlying the complexity of JA-mediated differential responses, which are important for plants to adapt their growth to the ever-changing environments.展开更多
Rauwolfia species(Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids(MIAs) such as reserpine,ajmalicine,ajmaline,serpentine and yohimbine.Reserpine,ajmalici...Rauwolfia species(Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids(MIAs) such as reserpine,ajmalicine,ajmaline,serpentine and yohimbine.Reserpine,ajmalicine and ajmaline are powerful antihypertensive,tranquilizing agents used in hypertension.Yohimbine is an aphrodisiac used in dietary supplements.As there is no report on the comparative and comprehensive phytochemical investigation of the roots of Rauwolfia species,we have developed an efficient and reliable liquid chromatography-tandem mass spectrometry(LC–MS/MS) method for ethanolic root extract of Rauwolfia species to elucidate the fragmentation pathways for dereplication of bioactive MIAs using highperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(HPLC–ESI–QTOF–MS/MS) in positive ion mode.We identified and established diagnostic fragment ions and fragmentation pathways using reserpine,ajmalicine,ajmaline,serpentine and yohimbine.The MS/MS spectra of reserpine,ajmalicine,and ajmaline showed C-ring-cleavage whereas E-ring cleavage was observed in serpentine via Retro Diels Alder(RDA).A total of 47 bioactive MIAs were identified and characterized on the basis of their molecular formula,exact mass measurements and MS/MS analysis.Reserpine,ajmalicine,ajmaline,serpentine and yohimbine were unambiguously identified by comparison with their authentic standards and other 42 MIAs were tentatively identified and characterized from the roots of Rauwolfia hookeri,Rauwolfia micrantha,Rauwolfia serpentina,Rauwolfia verticillata,Rauwolfia tetraphylla and Rauwolfia vomitoria.Application of LC–MS followed by principal component analysis(PCA) has been successfully used to discriminate among six Rauwolfia species.展开更多
Catharanthus roseus contains important anti-tumor terpenoid indole alkaloids (TIAs) such as vinblastine and vincristine. Cytochrome P450 enzyme geraniol 10-hydroxylase (G10H) is a putative rate-limiting enzyme involve...Catharanthus roseus contains important anti-tumor terpenoid indole alkaloids (TIAs) such as vinblastine and vincristine. Cytochrome P450 enzyme geraniol 10-hydroxylase (G10H) is a putative rate-limiting enzyme involved in the TIAs biosynthetic pathway in C. roseus. In this study the g10h gene driven by the cauliflower mosaic virus 35S (CaMV 35S) promoter was introduced into C. roseus through Agrobacterium-mediated transformation. The integration and overexpression of the target gene (g10h) in hairy root lines were confirmed by polymerase chain reaction and RT-QPCR analysis respectively. Overexpression of g10h in transgenic hairy root lines significantly enhanced the accumulations of monomeric alkaloid ajmalicine and dimeric alkaloids, vincristine and vinblastine. Total TIAs production in hairy roots reached (9.51) mg/g DW, over 3-fold higher than that in the untransformed root lines. This is the first report that engineering of g10h into TIAs-producing plant species results in significant enhancement of TIAs accumulation in cultured hairy roots. This study demonstrates that the putative rate-limiting step catalyzed by G10H is indeed the real rate-limiting step involved in the TIAs biosynthetic pathway in C. roseus, which is one of the key targets for promoting TIAs production by genetic engineering.展开更多
Medicinal plants have been used by marginal communities to treat various ailments. However, the potential of endophytes within these bio-prospective medicinal plants remains unknown. The present study elucidates the e...Medicinal plants have been used by marginal communities to treat various ailments. However, the potential of endophytes within these bio-prospective medicinal plants remains unknown. The present study elucidates the endophytic diversity of medicinal plants（Caralluma acutangula, Rhazya stricta, and Moringa peregrina） and the endophyte role in seed growth and oxidative stress. Various organs of medicinal plants yielded ten endophytes, which were identified as Phoma sp.（6 isolates）, Alternaria sp.（2）, Bipolaris sp.（1）, and Cladosporium sp.（1） based on 18 S rD NA sequencing and phylogenetic analysis. The culture filtrates（CFs; 25%, 50%, and 100% concentrations） from these endophytes were tested against the growth of normal and dwarf mutant rice lines. Endophytic CF exhibited dose-dependent growth stimulation and suppression effects. CF（100%） of Phoma sp. significantly increased rice seed germination and growth compared to controls and other endophytes. This growth-promoting effect was due to the presence of indole acetic acid in endophytic CF. The gas chromatography/mass spectrometry（GC/MS） analysis showed the highest indole acetic acid content（（54.31±0.21） μmol/L） in Bipolaris sp. In addition, the isolate of Bipolaris sp. exhibited significantly higher radical scavenging and anti-lipid peroxidation activity than the other isolates. Bipolaris sp. and Phoma sp. also exhibited significantly higher flavonoid and phenolic contents. The medicinal plants exhibited the presence of bio-prospective endophytic strains, which could be used for the improvement of crop growth and the mitigation of oxidative stresses.展开更多
An efficient protocol was developed for the synthesis of 3-aminoalkylated indoles using 3- chlorophenylboronic acid as a catalyst under ambient temperature conditions.The three-component reaction of indoles,aromatic a...An efficient protocol was developed for the synthesis of 3-aminoalkylated indoles using 3- chlorophenylboronic acid as a catalyst under ambient temperature conditions.The three-component reaction of indoles,aromatic aldehydes and N-methyl aniline offered corresponding 3-aminoalkylated indoles in excellent yields.This protocol presents some remarkable features such as mild reaction conditions,simple workup procedure and excellent yields.展开更多
To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines. METHODSChanges in cell proliferation and the cytotoxic effect of the test...To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines. METHODSChanges in cell proliferation and the cytotoxic effect of the tested compounds on human colorectal cancer cell lines and human fibroblasts were evaluated using MTS and BrdU assay, allowing us to choose the most potent substance. Cell cycle alterations were analyzed using flow cytometric analysis. The apoptosis-inducing effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI double staining using flow cytometry, as well as acridine orange/propidium iodide (AO/PI) staining. The flow cytometry method also allowed us to measure changes in levels or activation states of other factors associated with apoptosis, such as poly (ADP-ribose) polymerase (PARP), caspase-3 and -9, cytochrome c, Bcl-2 family proteins, and also the integrity of the mitochondrial membrane. To evaluate activity of the transcription factors and proteins involved in signaling pathways we used Western blot analysis together with flow cytometry. RESULTSAmong the ten tested compounds, compound K-453 {(±)-trans-1,2-dimethoxy-2’-(3,5-bis-trifluoromethylphenylamino)spiro{indoline-3,5’[4’,5’]dihydrothiazol} exhibited the most potent activity with IC<sub>50</sub> = 32.22 ± 1.14 μmol/L in human colorectal HCT116 cells and was thus selected for further studies. Flow cytometric analysis revealed a K-453-induced increase in the population of cells with sub-G<sub>1</sub> DNA content, which is considered as a marker of apoptotic cell death. The apoptosis-inducing effect of compound K453 was also confirmed by annexin V/PI double staining and AO/PI staining. The apoptosis was associated with the loss of mitochondrial membrane potential, PARP cleavage, caspase-3 and caspase-9 activation, release of cytochrome c, as well as changes in the levels of Bcl-2 family members. Moreover, flow cytometry showed that compound K-453 stimulates phosphorylation of p38 MAPK but decreases phosphorylation of Akt and Erk 1/2. Activation of p38 MAPK was also confirmed using Western blot analysis. This analysis also revealed down-regulation of NF-κB1 (p50) and RelA (p65) proteins and the loss of their anti-apoptotic activity. CONCLUSIONIn our study compound K-453 exhibited an antiproliferative effect by induction of intrinsic apoptosis as well as modulation of several signaling pathways.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82273845,82304331,and 82360695)Guangxi Natural Science Foundation project(No.2023GXNSFBA026305).
文摘Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products social molecular networking(OSMAC-GNPS)strategy,a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp.EGF 15-0-3.Structurally,sterpiperazines A(1)and B(2)represent the first steroid-based indole alkaloids with unprecedented backbones.Biologically,compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1(Tdp1)inhibitor with a unique mechanism distinct from the reported modulators,and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.
文摘Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,which utilize vinylene carbonate as a new C2 synthon.This protocol is expected to provide a facile and useful access to various indole derivatives.
文摘Difluoromethyl compounds are widely found in natural products,bioactive molecule and pharmaceuticals.A visible-light induced difluoromethylation/cyclization of 2-aryl indoles is described to construct indolo[2,1-a]isoquinolin-6(5H)-one derivatives using the inexpensive and easy-to-handle HCF_(2)SO_(2)Na as an HCF2 sources.Diverse difluoromethylated indolo[2,1-a]isoquinolines were readily obtained in moderate to good yields.Mechanistic studies demonstrate that the reaction may involve a radical process.
文摘multi-component reaction was reported for the synthesis of 7-ester indoles and bis-indoles under microwave-assisted conditions,enriching and expanding the library of heterocyclic compounds.This reaction started from enamine ketone,aromatic ketone aldehyde hydrate,and carboxylic acid,and selectively synthesized 7-ester indoles and bis-indoles by changing the substituted enamine ketone substrate.This method had the characteristics of high regional selectivity,short reaction time,and green environmental protection.
文摘Indole[2,1-α]isoquinolines are an important class of bioactive molecules and show good antibacterial activity.In the present study,an efficient copper(I)-catalyzed acylation/cyclization has been developed for the construction of indolo[2,1-α]isoquinoline derivatives by utilizing 2-aryl-N-acryloyl indole and benzohydrazide as reactants in the presence of CuI as catalyst and tert-butyl hydroperoxide as oxidant.The present protocol exhibits good functional group tolerance,and a series of acylated indole[2,1-α]isoquinolines were synthesized in moderate to good yields.Radical trapping experiments indicated that the reaction may involve a radical process.
文摘Cycloheptatriene is a privileged structural motif present in many bioactive compounds,pharmaceutical agents and natural products,especially in a large number of core structures of sesquiterpenoids.Herein,a mild and efficient synthetic approach was reported for access of a series of C2 or C3-(cycloheptatrienyl)-substituted indoles.A wide range of functional groups can be well tolerated in this transformation,especially including hydroxyl,halo,carboxylic acid and its derivative groups.Based on these results,a rational mechanism via electrophilic substitution of indoles with tropylium tetrafluoroborate is proposed.
文摘Zeng N,Ye G,Zheng M,Liu G,Zhang S,Ma S,Xia Z,Zhou Y,Wang S,Xia Q.Discovery and validation of indole nitroolefins as novel covalent GPX4 inhibitors for inducing ferroptosis in urological cancers.Chin J Cancer Res 2025;37(3):404-416.doi:10.21147/j.issn.1000-9604.2025.03.09.
基金Supported by the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(No.LR20C190001)the National Natural Science Foundation of China(No.42376103)+1 种基金the Natural Science Foundation of Ningbo City(No.2021J062)the K.C.Wong Magna Fund in Ningbo University。
文摘Recently,more and more bacteria have been reported to become tolerant to antibiotics.In this study,one tnaA gene involved in indole production,and the effect of exogenous indole on the formation of persister cells specific to tetracycline in Vibrio splendidus were characterized.The tnaA Vs gene was first cloned and conditionally expressed in Escherichia coli Rosetta(DE3).To investigate the regulatory effect of TnaA Vs,the tnaA deletion strain AJ01/ΔtnaA was constructed by in-frame deletion.The undetected extracellular indole in the AJ01/ΔtnaA indicated that TnaA was the solo enzyme to produce indole in V.splendidus.The drop plate method showed that AJ01/ΔtnaA was more tolerant to the higher concentration of tetracycline than that of AJ01,being 340-fold higher in the proportion of survived cells when cell density OD 600≈0.65.Moreover,the synergistic effects of indole and tetracycline on killing of V.splendidus were determined.Results show that addition of 2-mmol/L indole increased the susceptibility of both AJ01 and AJ01/ΔtnaA to 10×minimum inhibitory concentration tetracycline.To explore the genes and pathways regulated by TnaA Vs,the transcriptomic analysis between AJ01 and AJ01/ΔtnaA was performed.Result shows that TCA cycle,arginine biosynthesis,quorum sensing and microbial metabolism in diverse environments were downregulated,while the ribosome pathways,the protein metabolic process,peptide biosynthetic and metabolic process were upregulated in the AJ01/ΔtnaA.This study shows that indole could enhance the bactericidal effect of tetracycline on V.splendidus by decreased ribosome level probably but increased ATP level.
文摘Skeletal editing has emerged as a powerful tool in organic chemistry,enabling the simplification of synthetic routes to complex molecules[1].Indoles,electron-rich nitrogen-containing building blocks,represent privileged scaffolds prevalent in pharmaceuticals,natural products,and bioactive compounds.The application of skeletal editing strategies to modify such structures is highly valuable and in growing demand.Leveraging the electronrich nature of indoles at C2 and C3,single-carbon atom insertion using cationic carbyne equivalents offers an efficient approach for indole ring expansion to quinoline(Scheme 1a).However,existing methods predominantly rely on halocarbene precursors,which restricts the functional groups of ring-expanded products to halogen[2],alkyl,aryl,heteroaryl and ester moieties[3].This limitation hinders their utility in late-stage skeletal modifications of complex targets.
基金Supported by Key Disciplines of The Sixth Cycle of Tongji Hospital,No.ZDTS24-BLShanghai Municipal Science and Technology Commission 2021"Science and Technology Innovation Action Plan"Medical Innovation Research Project,No.21Y11908800Clinical Research Project of Tongji Hospital of Tongji University,No.ITJ(ZD)2206.
文摘BACKGROUND Indolent T-cell lymphoma of the gastrointestinal tract(iTCL-GI)is a rare mature T-cell lymphoma that has been formally recognized as a distinct entity in the 5th Edition World Health Organization Classification of Tumours of Haematolymphoid Tumours.However,the coexistence of iTCL-GI with epithelial malignancies is rare in clinical practice.This study reports a case of iTCL-GI with gastric signet-ring cell carcinoma(SRCC).We aim to increase diagnostic awareness among clinicians and pathologists regarding multiple primary tumors.CASE SUMMARY A 65-year-old female presented with a 5-month history of lower abdominal pain,bloating,and vomiting.An abdominal computed tomography scan revealed irregular thickening of the gastric wall.Endoscopy revealed diffuse mucosal edema and rigid mucosa along the lesser curvature of the gastric body.There was a 1.5 cm mucosal protrusion on the greater curvature.Biopsy revealed that the lamina propria was expanded by a dense,nondestructive infiltrate of small lymphocytes in the greater curvature,which were characterized by a CD3+/CD8+/TIA-1+immunophenotype with a low Ki-67 index.Clonal T-cell receptor rearrangement was detected,but the Epstein-Barr virus encoded RNA's was negative.Lesions on the lesser curvature of the gastric body were confirmed to be SRCCs.After three months of follow-up,the patient completed four cycles of chemotherapy targeting the SRCC.While her abdominal pain improved,she experienced a weight loss of 5 kg.CONCLUSION Clinicians and pathologists must integrate assessment of these rare cases to prevent misdiagnosis and guide clinical practice.
基金Supported by The National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-132.
文摘BACKGROUND Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract(iNKLPD)is a rare and recently defined entity,recognized in the 2022 WHO classification of hematolymphoid tumors.iNKLPD typically exhibits a benign or slowly progressive clinical course,with disease localized to the gastrointestinal tract.Here,we present what we believe to be the first reported case of iNKLPD associated with protein-losing enteropathy(PLE),characterized by a poor response to chemotherapy and rapid clinical deterioration,culminating in death within a few months.CASE SUMMARY We report the case of a 64-year-old man who presented with bilateral lower-extremity edema and fatigue.Laboratory tests revealed marked hypoalbuminemia,while other liver function parameters remained within normal limits.Renal and cardiac function assessments were unremarkable.Histopathological examination of endoscopic biopsies confirmed a diagnosis of iNKLPD of the gastrointestinal tract.The patient was treated with oral prednisone and cyclosporine,which led to temporary improvement in both symptoms and serum albumin levels.However,disease relapse occurred during corticosteroid tapering,accompanied by worsening hypoalbu-minemia and refractory diarrhea.The patient died eight months after diagnosis,likely due to disease progression or severe treatment-related complications.CONCLUSION iNKLPD generally exhibits an indolent course;nonetheless,the prognosis may be poor if secondary PLE is involved.
文摘Nanosized fibrous cerium（IV） hydrogen phosphate membrane, Ce（HPO4）2·2.9H20 （nCePf）, was prepared and characterized by chemical, XRD （X-ray diffraction）, TGA （thermogravimetric analysis）, SEM （scanning electron microscopy） and TEM （transmission electron microscopy）. Novel supported nanofibrous Ce（IV） phosphate/polyiondole nanocomposite membranes were prepared via in-situ chemical oxidation of the monomer that was promoted by the reduction of Ce（IV） ions present in the inorganic matrix. The presence of Ce（IV） ions allows redox reactions necessary to oxidative polymerization to occur. The resultant material was characterized by TGA, elemental （C, H, N） analysis and FT-IR （Fourier transform spectroscopy）. SEM images of the resulting nanocomposite reveals a uniform distribution of the polymer on the inorganic matrix. Amount of polyindole polymer present in the composite is found to be - 7.0%.
基金National Natural Science Foundation of China(Grant No.30973628)
文摘From the aerial parts ofNauclea officinalis （Pierre ex Pitard） Merr. et Churl, one new indole alkaloid paratunamide E （1） has been isolated together with six known indole alkaloids, paratunamide A （2）, nauclealotide C （3）, nauclealotide A （4）, vincosamide （5）, strictosamide （6） and naucleamide F （7）. Naucleamide F （7） was isolated from Nauclea officinalis for the first time. All of the seven compounds above were elucidated by spectroscopic methods including 1 D and 2 D NMR soectroscoDic analyses.
基金We gratefully acknowledge Dr Jianru Zuo （Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China） for providing T-DNA mutagenized population of Arabidopsis, Dr Salome Prat （Institut de Biologia Molecular de Barcelona, Spain） for providing homozygous atmyc2-2 mutant （T-DNA insertion line SALK_083483） seeds and Dr Jane Glazebrook for assisting with camalexin measurements. This work was supported by grants from the Chinese Academy of Sciences （KSCX2- YW-N-045, KSCX2-YW-N-015）, the Ministry of Agriculture of China （2008ZX08009-003-001） and the Ministry of Science and Technology of China （2007CB948201, 2006AA10A116）. Work in the laboratory of Jerry D Cohen was supported by grants from the US National Science Foundation （MCB-0725149 and DBI- PGRP-0606666） and the USDA, National Research Initiative （2005-35318-16197）.
文摘Jasmonic acid （JA） is a fatty acid-derived signaling molecule that regulates a broad range of plant defense responses against herbivores and some microbial pathogens. Molecular genetic studies have established that JA also performs a critical role in several aspects of plant development. Here, we describe the characterization of the Arabidopsis mutantjasmonic acid-hypersensitivel-1 （jah1-1）, which is defective in several aspects of JA responses. Although the mutant exhibits increased sensitivity to JA in root growth inhibition, it shows decreased expression of JA-inducible defense genes and reduced resistance to the necrotrophic fungus Botrytis cinerea. Gene cloning studies indicate that these defects are caused by a mutation in the cytochrome P450 protein CYP82C2. We provide evidence showing that the compromised resistance of thejah1-1 mutant to B. cinerea is accompanied by decreased expression of JA-induced defense genes and reduced accumulation of JA-induced indole glucosinolates （IGs）. Conversely, the enhanced resistance to B. cinerea in CYP82C2-overexpressing plants is accompanied by increased expression of JA-induced defense genes and elevated levels of JA-induced IGs. We demonstrate that CYP82C2 affects JA-induced accumulation of the IG biosynthetic precursor tryptophan （Trp）, but not the JA-induced IAA or pathogen-induced camalexin. Together, our results support a hypothesis that CYP82C2 may act in the metabolism of Trp-derived secondary metabolites under conditions in which JA levels are elevated. Thejah1-1 mutant should thus be important in future studies toward understanding the mechanisms underlying the complexity of JA-mediated differential responses, which are important for plants to adapt their growth to the ever-changing environments.
基金Council of Scientific Industrial Research,India for providing financial support
文摘Rauwolfia species(Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids(MIAs) such as reserpine,ajmalicine,ajmaline,serpentine and yohimbine.Reserpine,ajmalicine and ajmaline are powerful antihypertensive,tranquilizing agents used in hypertension.Yohimbine is an aphrodisiac used in dietary supplements.As there is no report on the comparative and comprehensive phytochemical investigation of the roots of Rauwolfia species,we have developed an efficient and reliable liquid chromatography-tandem mass spectrometry(LC–MS/MS) method for ethanolic root extract of Rauwolfia species to elucidate the fragmentation pathways for dereplication of bioactive MIAs using highperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(HPLC–ESI–QTOF–MS/MS) in positive ion mode.We identified and established diagnostic fragment ions and fragmentation pathways using reserpine,ajmalicine,ajmaline,serpentine and yohimbine.The MS/MS spectra of reserpine,ajmalicine,and ajmaline showed C-ring-cleavage whereas E-ring cleavage was observed in serpentine via Retro Diels Alder(RDA).A total of 47 bioactive MIAs were identified and characterized on the basis of their molecular formula,exact mass measurements and MS/MS analysis.Reserpine,ajmalicine,ajmaline,serpentine and yohimbine were unambiguously identified by comparison with their authentic standards and other 42 MIAs were tentatively identified and characterized from the roots of Rauwolfia hookeri,Rauwolfia micrantha,Rauwolfia serpentina,Rauwolfia verticillata,Rauwolfia tetraphylla and Rauwolfia vomitoria.Application of LC–MS followed by principal component analysis(PCA) has been successfully used to discriminate among six Rauwolfia species.
基金Item supported by China national"863"high-tech program (2002AA212191)China ministry of educa-tion and science and technology commission of Shanghai(04XD14011)
文摘Catharanthus roseus contains important anti-tumor terpenoid indole alkaloids (TIAs) such as vinblastine and vincristine. Cytochrome P450 enzyme geraniol 10-hydroxylase (G10H) is a putative rate-limiting enzyme involved in the TIAs biosynthetic pathway in C. roseus. In this study the g10h gene driven by the cauliflower mosaic virus 35S (CaMV 35S) promoter was introduced into C. roseus through Agrobacterium-mediated transformation. The integration and overexpression of the target gene (g10h) in hairy root lines were confirmed by polymerase chain reaction and RT-QPCR analysis respectively. Overexpression of g10h in transgenic hairy root lines significantly enhanced the accumulations of monomeric alkaloid ajmalicine and dimeric alkaloids, vincristine and vinblastine. Total TIAs production in hairy roots reached (9.51) mg/g DW, over 3-fold higher than that in the untransformed root lines. This is the first report that engineering of g10h into TIAs-producing plant species results in significant enhancement of TIAs accumulation in cultured hairy roots. This study demonstrates that the putative rate-limiting step catalyzed by G10H is indeed the real rate-limiting step involved in the TIAs biosynthetic pathway in C. roseus, which is one of the key targets for promoting TIAs production by genetic engineering.
基金Project supported by the Oman Research Council(FURAP Program)the Korea Institute of Planning and Evaluation for Technology in Food,Agriculture,Forestry and Fisheries(IPET) through Agriculture,Food and Rural Affairs Research Center Support Program,funded by Ministry of Agriculture,Food and Rural Affairs(MAFRA)(716001-7)
文摘Medicinal plants have been used by marginal communities to treat various ailments. However, the potential of endophytes within these bio-prospective medicinal plants remains unknown. The present study elucidates the endophytic diversity of medicinal plants（Caralluma acutangula, Rhazya stricta, and Moringa peregrina） and the endophyte role in seed growth and oxidative stress. Various organs of medicinal plants yielded ten endophytes, which were identified as Phoma sp.（6 isolates）, Alternaria sp.（2）, Bipolaris sp.（1）, and Cladosporium sp.（1） based on 18 S rD NA sequencing and phylogenetic analysis. The culture filtrates（CFs; 25%, 50%, and 100% concentrations） from these endophytes were tested against the growth of normal and dwarf mutant rice lines. Endophytic CF exhibited dose-dependent growth stimulation and suppression effects. CF（100%） of Phoma sp. significantly increased rice seed germination and growth compared to controls and other endophytes. This growth-promoting effect was due to the presence of indole acetic acid in endophytic CF. The gas chromatography/mass spectrometry（GC/MS） analysis showed the highest indole acetic acid content（（54.31±0.21） μmol/L） in Bipolaris sp. In addition, the isolate of Bipolaris sp. exhibited significantly higher radical scavenging and anti-lipid peroxidation activity than the other isolates. Bipolaris sp. and Phoma sp. also exhibited significantly higher flavonoid and phenolic contents. The medicinal plants exhibited the presence of bio-prospective endophytic strains, which could be used for the improvement of crop growth and the mitigation of oxidative stresses.
基金Dr.P.L.More and Dr.W.N.Jadhav,Dnyanopasak College,Parbhani for providing necessary facilities and Financial support for this work by DST-SERC,New Delhi(SR/FT/CS- 023/2008) is highly appreciated
文摘An efficient protocol was developed for the synthesis of 3-aminoalkylated indoles using 3- chlorophenylboronic acid as a catalyst under ambient temperature conditions.The three-component reaction of indoles,aromatic aldehydes and N-methyl aniline offered corresponding 3-aminoalkylated indoles in excellent yields.This protocol presents some remarkable features such as mild reaction conditions,simple workup procedure and excellent yields.
文摘To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines. METHODSChanges in cell proliferation and the cytotoxic effect of the tested compounds on human colorectal cancer cell lines and human fibroblasts were evaluated using MTS and BrdU assay, allowing us to choose the most potent substance. Cell cycle alterations were analyzed using flow cytometric analysis. The apoptosis-inducing effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI double staining using flow cytometry, as well as acridine orange/propidium iodide (AO/PI) staining. The flow cytometry method also allowed us to measure changes in levels or activation states of other factors associated with apoptosis, such as poly (ADP-ribose) polymerase (PARP), caspase-3 and -9, cytochrome c, Bcl-2 family proteins, and also the integrity of the mitochondrial membrane. To evaluate activity of the transcription factors and proteins involved in signaling pathways we used Western blot analysis together with flow cytometry. RESULTSAmong the ten tested compounds, compound K-453 {(±)-trans-1,2-dimethoxy-2’-(3,5-bis-trifluoromethylphenylamino)spiro{indoline-3,5’[4’,5’]dihydrothiazol} exhibited the most potent activity with IC<sub>50</sub> = 32.22 ± 1.14 μmol/L in human colorectal HCT116 cells and was thus selected for further studies. Flow cytometric analysis revealed a K-453-induced increase in the population of cells with sub-G<sub>1</sub> DNA content, which is considered as a marker of apoptotic cell death. The apoptosis-inducing effect of compound K453 was also confirmed by annexin V/PI double staining and AO/PI staining. The apoptosis was associated with the loss of mitochondrial membrane potential, PARP cleavage, caspase-3 and caspase-9 activation, release of cytochrome c, as well as changes in the levels of Bcl-2 family members. Moreover, flow cytometry showed that compound K-453 stimulates phosphorylation of p38 MAPK but decreases phosphorylation of Akt and Erk 1/2. Activation of p38 MAPK was also confirmed using Western blot analysis. This analysis also revealed down-regulation of NF-κB1 (p50) and RelA (p65) proteins and the loss of their anti-apoptotic activity. CONCLUSIONIn our study compound K-453 exhibited an antiproliferative effect by induction of intrinsic apoptosis as well as modulation of several signaling pathways.
