MOLECULES
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2018
·Vol. 23
·期 3
·582
·
IF 3.098
Lunqiang Jin,Feng Liang
Increasing interests have been invested in the development of synthetic strategies toward the construction of spiro[pyrrolidine-2,3′-oxindole], which is the core structural skeleton in some compounds with diverse biological activities. In this work, an efficient diastereoselective 1,3-dipolar cycloaddition reaction of azomethine ylides generated in situ from 3-amino oxindoles and aldehydes with maleimides has been described. The protocol provides a facile and efficient access to structurally diverse succinimide-fused spiro[pyrrolidine-2,3′-oxindole] compounds in good to high yields (up to 93%) with moderate to excellent diastereoselectivities (up to >95:5). The relative stereochemistry of cycloaddition products has been assigned by X-ray diffraction analysis.Keywords:1,3-dipolar cycloaddition;azomethine ylide;one pot synthesis;maleimide;succinimide-fused spiro[pyrrolidine-2,3′-oxindole]
研究领域:
有机化学
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药物化学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Zu-Sheng Huang,Xu-Feng Zang,Tao Hua,Lingyun Wang,Herbert Meier,Derong Cao
Five novel metal-free organic dyes DQ1–5 containing a dipentyldithieno[3,2-f:2′,3′-h]quinoxaline (DPQ) unit were synthesized and applied in dye-sensitized solar cells (DSSCs), where DPQ was employed as a π-spacer for the first time. Their photophysical, electrochemical, and theoretical calculations and photovoltaic properties were systematically investigated. All the five dyes show broad photoresponse. Especially the absorption edges of DQ3–5 extend to 800 nm on the TiO2 films. The inserted electron-rich unit 3,4-ethylenedioxythiophene or electron-withdrawing group benzothiadiazole (BTD) in DPQ-based dyes can greatly influence the optoelectronic properties of the dyes. In addition, the different electron donors also significantly affect the performance of the DSSCs. Under standard global AM 1.5 solar light conditions, the DQ5 sensitized solar cell obtained a power conversion efficiency of 7.12%. The result indicates that the rigid DPQ-based organic dye is a promising candidate for efficient DSSCs.
研究领域:
材料科学
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能源科学
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DOI
高影响因子
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
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2023
·
IF 1.9
Wenchao Pan,Yadong Wang,Caiyan Zhao
Objective To explore the protective effect and related mechanism of miR-140-5p on liver fibrosis by interfering with TGF-β/Smad signaling pathway.Methods Liver fibrosis mice models were established by intraperitoneal injection of CCL4. Hematoxylin and eosin (HE) staining was used to detect the structural and morphological changes of the liver. Masson staining was used to detect collagen deposition. Human hepatic stellate cells (HSCs, LX-2) were transfected with miR-140-5p mimic or inhibitor then treated with TGF-β1. The qRT-PCR and Western blotting was used to detect the expression of related molecules. The luciferase reporter assay was used to identify the target of miR-140-5p.Results Our results indicated that miR-140-5p expression was downregulated in fibrotic liver tissues of model mice and LX-2 cells treated with TGF-β1. The overexpression of miR-140-5p decreased the expression of collagen1(COL1) and α-smooth muscle actin(α-SMA), inhibited the phosphorylation of Smad-2/3 (pSmad-2/3) in LX-2 cells. Conversely, the knockdown of miR-140-5p upregulated COL1 and α-SMA expression, increased Smad-2/3 phosphorylation. A dual-luciferase reporter assay showed that TGFβR1 was a target gene of miR-140-5p. The overexpression of miR-140-5p suppressed TGFβR1 expression in LX-2 cells. Additionally, knockdown of TGFβR1 decreased the expression of COL1 and α-SMA. Conversely, the overexpression of TGFβR1 reversed the inhibitory effect of miR-140-5p upregulation on expression of COL1 and α-SMA.Conclusion miR-140-5p bound to TGFβR1 mRNA 3′-untranslated region(3′UTR) and inhibited the expression of TGFβR1, pSmad-2/3, COL1 and α-SMA, thereby exerting a potential therapeutic effect on hepatic fibrosis.
研究领域:
分子生物学
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肝病学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Peng Zhu,You Yang,Jianqiang Qian,Jun Han,Dairui Kong,Bo Sun,Jian Zhang,Jingtao Wei,Qulian Guo,Sihui Nian,Lixiang Zhou,Guodong Wang,Shaohua Hou
Mitogen-activated protein kinase–interacting kinases (MNKs) play a key role in the occurrence and migration of tumors and have become promising targets for tumor therapy. Nevertheless, the development progress on the MNKs inhibitors against cancer was relatively slow. In this study, compound 4s (MNK1/2 half-maximal inhibitory concentration [IC 50 ] = 987/1048 nM), a promising MNKs inhibitor was discovered based on virtual screening. After the structural optimization of compound 4s , 18 novel thiophene [2,3-D] pyrimidine–thiazole derivatives were designed and prepared, and their inhibitory effect on MNKs was determined. Among which, compound 5l exhibited the best inhibitory activity on MNKs (MNK1/2 IC 50 = 23/62 nM) and relatively high selectivity among 125 kinases. Results from in vitro experiments indicated that compound 5l could significantly inhibit the in vitro proliferation (IC 50 = 0.8 ± 0.1 μM) and migration of breast cancer cells, which demonstrated that compound 5l is a promising MNK inhibitor to treat breast cancer and need further study.
研究领域:
药理学
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肿瘤学
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药物化学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Yunchang Fan,Qiang Zhou,Sheli Zhang,Yanhe Nie
Thiosulfate has been considered as a more environmentally-friendly alternative to cyanide salts for the extraction of gold from gold ores and the development of affordable, green and efficient adsorbents for the isolation of gold-thiosulfate complex (Au(S 2 O 3 ) 2 3− ) from the leaching solution remains a significant challenge. To address this issue, chitosan, a natural macromolecule , was selected as a carrier and chemically modified with ionic liquids . The ionic liquids modified chitosan showed greater adsorption capacity towards Au(S 2 O 3 ) 2 3− compared with pristine chitosan. The adsorption of Au(S 2 O 3 ) 2 3− on ionic liquid modified chitosan followed Freundlich isotherm and pseudo-second order kinetic models, involving an anion-exchange mechanism with liquid film diffusion as the rate-limiting step. The chitosan modified with butylimidazolium-based ionic liquid had an adsorption capacity of 5.0 mg g −1 for gold (10 mg L −1 of gold, pH 6, 2 g L −1 of adsorbent dosage), outperforming other reported adsorbents. The ionic liquid modified chitosan showed a high adsorption efficiency of up to 96.7 % for Au(S 2 O 3 ) 2 3− in an actual thiosulfate leaching solution with a desorption efficiency of 98.4 %, suggesting that the ionic liquid modified chitosan has the potential to be a eco-friendly, biocompatible and effective adsorbent for the recovery of Au(S 2 O 3 ) 2 3− .
研究领域:
环境科学
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材料科学
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化学工程
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DOI
PubMed
高影响因子
Ceramics-Switzerland
·
2024
·Vol. 7
·期 1
·426-435
·
IF 2.7
Yuan-Bin Chen,Yu Fan,Shiuan-Ho Chang,Shaobing Shen
In this study, we used solid-state synthesis to prepare Ba[(ZnxCo1−x)1/3(Nb0.5Ta0.5)2/3]O3microwave ceramics for mobile communications. Compared with Ba[Zn1/3(Nb0.5Ta0.5)2/3]O3, in the prepared materials, Co2+substitution with Zn2+improved the Q × f value and enabled densification and sintering at a lower temperature. We used X-ray diffraction (XRD) and scanning electron microscopy (SEM) to analyze the obtained microstructure. Ba[(ZnxCo1−x)1/3(Nb0.5Ta0.5)2/3]O3was found to have a 1:2 ordered hexagonal structure, and its Q × f value increased with the increase in sintering temperature. In this work, excellent microwave dielectric properties—τf= −0.7 ppm/°C, εr= 34.5, and Q × f = 110,000 GHz—were obtained by sintering Ba[(Zn0.3Co0.7)1/3(Nb0.5Ta0.5)2/3]O3at 1400 °C for 5 h.
研究领域:
材料科学
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电子工程
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DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
·
IF 11.467
Hong Liu,Zhitao Hu,Haolin Chen,Yanzi Yan,Zhicheng Le,Cong Wei,Wenqiang Cao,Tianfeng Chen,Yongming Chen,Lixin Liu
Vaccination with subunit nanovaccines is a promising strategy to combat virus infection and tumor development. However, immunogenicity of present nanovaccines is still unsatisfied for clinical translation. Here, we developed a nanovaccine loading a STING agonist, 2′3′-cGAMP and, a model subunit antigen, OVA , by using a well-defined self-degradable poly(β-amino ester)s to treat B16F10-OVA melanoma tumors. The polymer underwent slow hydrolysis at pH 5.5 but self-degraded induced by the amino groups along the polyester chain at pH > 6.5. It is shown that the self-degradation products facilitated the release of 2′3′-cGAMP and OVA from early endolysome to the cytosol, where the two components strongly activated CD8 + T lymphocytes (CTLs) and significantly enhanced Ifn1, TNF , Cxcl9, and Cxcl10 expression. In turn, the tumor microenvironment was remolded from cold to hot. Moreover, the nanovaccine could be quickly drained to sentinel lymph nodes after intratumoral injection. The nanovaccine with strong immunogenicity also could reduce the side effects of systemic inflammatory reaction caused by molecular 2′3′-cGAMP. The tumor progression of animals was inhibited, and their survival rates increased significantly. Thus, the multifunctional biodegradable material provided a new delivery system for a cancer vaccine to translate to clinics.
研究领域:
癌症研究
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免疫学
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生物医学工程
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分子生物学
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DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2021
·Vol. 50
·期 29
·10206-10213
·
IF 4.39
Wenyao Zhang,Wenqi Jin,Meng Cheng,Ruonan Zhang,Zhihua Yang,Shilie Pan
Fluorine-containing compounds significantly enrich the diversity of inorganic chemical structures. Here, four alkaline-earth metal difluorophosphates with different space groups, namely NH4Mg(PO2F2)3 (Cmcm) (1), NH4Sr(PO2F2)3 (P) (2), (NH4)2Ba(PO2F2)4 (P2/n) (3) and Ba(PO2F2)2 (I2d) (4), were synthesized and their structures were determined for the first time. 4 is not only the first alkaline-earth-metal difluorophosphate, but also the first difluorophosphate reported to crystallize in the non-centrosymmetric space group I2d of the tetragonal crystal system. All of the three-dimensional (3D) structures of the title compounds consist of isolated (PO2F2)−, AE–O and NH4+ units, while the differences of the cation radius result in various arrangements of the (PO2F2)− units, which leads to diverse crystal structures and the disparate optical anisotropy of the crystals. According to the deep-ultraviolet (DUV) transmittance spectrum, 3 exhibits a short DUV cut off edge (<180 nm). Solid state 19F and 31P magic-angle spinning NMR spectroscopy was used to verify the presence of covalent P–F bonds in 3. The different size effects, as well as the coordination environments of the Mg2+, Sr2+, and Ba2+ cations, on the structures as a whole have been discussed in detail. In addition, the calculated birefringence values were observed to differ from 0.011 to 0.033 for the four compounds.
研究领域:
无机化学
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材料科学
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光学
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DOI
PubMed
高影响因子
ANALYST
·
2017
·Vol. 142
·期 19
·3733-3739
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IF 3.885
Jing Li,Meng Cheng,Mei-Jin Li
A sensitive assay was demonstrated for the colorimetric and luminescent detection of heparin. Positively charged [Ru(phen)2np]2+ (np: naphtho[2,3-f][1,10]phenanthroline) can interact with negatively charged AuNPs through electrostatic interaction, leading to the luminescence quenching of [Ru(phen)2np]2+via energy transfer as well as the aggregation of AuNPs together with a color change in solution from red to blue. Upon the addition of negatively charged heparin to gold nanoparticles functionalized by ruthenium(II) complexes, the emission of [Ru(phen)2np]2+ recovered due to the competitive adsorption of [Ru(phen)2np]2+ to heparin and AuNPs. A linear calibration curve was obtained in the 0.4 μM to 100 μM range and 0.1 μM to 6 μM with a low detection limit of 0.22 μM and 0.024 μM based on 3σ/s for heparin quantification in buffer solution and in 1% fetal bovine serum (FBS), respectively. Interestingly, the naked eye alone can judge the presence of 0.02 μM heparin without the aid of any advanced instruments by color change. Thus a convenient and visual method to detect heparin was established.
研究领域:
分析化学
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纳米技术
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生物化学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Chemistry
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2021
·
IF 2.506
Yuqing Wang,Jianming Wu,Yunxia Li,Jing Yang,Long Wang,Anguo Wu,Feihong Huang,Nan Jiang,Can Tang,Yan Li
To investigate the pharmacokinetics of 2, 3, 8-trimethylellagic (TMEA) in rats in vivo and determine the possible effects of the pathological conditions and compatibility, a rapid and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for quantitative determination was developed. TMEA and Artemetin (internal standard, IS) were separated on an Acquity Shim-pack GIST column with a total running time of 7 min using gradient elution at a flow rate of 0.3 mL/min. The intraday and interday relative standard deviations were <9.50%, and the relative error of accuracy was between −5.70% and 2.96%. The calibration curve of TMEA demonstrated good linearity with r2 = 0.9996, with the average recovery changing from 94.77% to 102.47% and the matrix effect from 93.16% to 100.15%. Compared with the normal group, the area under the plasma concentration-time curve from time 0 to the last time of quantifiable concentration (AUC(0 − t)), area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUC(0 − ∞)), and the maximum concentration (Cmax) of TMEA increased, whereas the time of maximum concentration (Tmax) and apparent clearance (CL/F) remarkably decreased in the TMEA group. With significantly reduced CL/F, AUC(0 − t), AUC(0 − ∞), and Cmax for TMEA were increased approximately one time after combining with 3, 7-Di-O-methylducheside A (DOMA). AUC(0 − t) and Cmax for TMEA in the 2, 3, 8-trimethylellagic-3, 8-dimethoxyellagic acid-2-oxyglucoside (TMEA-DMAG) group were significantly lower than that in the TMEA group with clearly prolonged Tmax and increased CL/F. These findings indicate that the changes in the pharmacokinetic parameters of TMEA may be caused by pathological and combination conditions.
研究领域:
药理学
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分析化学
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中药学
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DOI
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 60
·34912-34925
·
IF 3.049
Shou-Jie Shen,Xiao-Li Du,Xiao-Li Xu,Yue-Hua Wu,Ming-gang Zhao,Jin-Yan Liang
The first sequentially combined inorganic base promoted N-addition/[2,3]-sigmatropic rearrangement reaction of α-alkylidene pyrazolinones and propargyl sulfonium salts has been reported to construct homoallyl sulfur-containing pyrazolones with moderate to excellent yields. α-Alkylidene pyrazolinones function as N-nucleophilic agents distinguished from the reported C-addition reactions. Propargyl sulfonium salts were first involved in the [2,3]-sigmatropic rearrangement protocol differentiated from the well-established annulation reactions. The excellent regioselectivity, the broad scope of substrates, gram-scale synthesis and convenient transformation embody the synthetic superiority of this cascade process.
研究领域:
有机化学
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合成化学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2022
·
IF 7.088
Zhendong Song,Linlin Lou,Guangjin Fan,Lu Liu,Yang Ge,He Liu,Albert S.C. Chan,Xiaolei Zhang,Xiao-Feng Xiong
Oncogene KRAS plays predominant roles in human cancers by regulating cell proliferation , differentiation, and migration. Recent progress revealed that directly target KRAS G12C with allosteric inhibitors that covalently bind to the switch Ⅱ pocket is feasible. Herein, series of pyrrolo[2,3- d ]pyrimidine derivatives were designed and synthesized through systematic structural optimization, leading to the discovery of compound 2-(( S )-1-acryloyl-4-(2-((( 2R , 7aS )-2-fluorohexahydro-1 H -pyrrolizin-7a(5 H )-yl)methoxy)-7-methyl-6-(8-methylnaphthalen-1-yl)-7 H -pyrrolo[2,3- d ]pyrimidin-4-yl)piperazin-2-yl)acetonitrile ( 50 ) with high KRAS/SOS1 inhibitory potency (IC 50 = 0.21 μM) and strong anti-proliferation activities on cancer cells harboring KRAS p.G12C . Compound 50 also exhibited satisfactory selectivity , moderate pharmacokinetic characters, and good anticancer effects in vivo . Meaningfully, the identification of these compounds highlights the necessity of an appropriate conformational constraint for acquiring the applicable binding pose in the cryptic pocket of KRAS, and the results support efforts toward design of KRAS inhibitors with novel skeleton and binding mechanism could be beneficial for targeting the acquired drug resistance.
研究领域:
肿瘤学
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药理学
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）