JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2021
·
IF 5.051
Heping Zhu,Shilong Ying,Bingluo Zhou,Xinyang Hu,Xiao Liang,Wangyu Li,Dungai Wang,Hongchuan Jin,Yuanjiang Pan
Colorectal cancer (CRC) is a common malignant tumour of human digestive tract. The high mortality rate of CRC is closely related to the limitations of existing treatments. Thus, there is an urgent need to search for new anti-CRC agents. In this work, twenty novel coumarin-dithiocarbamate derivatives (IDs) were designed, synthesized and evaluated in vitro. The results suggest that the most active compound ID-11 effectively inhibited the proliferation of CRC cell lines while shown little impact on normal colon epithelial cells. Mechanism studies revealed that ID-11 displayed bromodomain-containing protein 4 inhibitory activity, and induced G2/M phase arrest, apoptosis as well as decreased the expression levels of the key genes such as c-Myc and Bcl-2 in CRC cell lines. Moreover, the ADMET properties prediction results shown that ID-11 possess well metabolic characteristics without obvious toxicities. Our data demonstrated that compound ID-11 may be a promising anti-CRC agent and deserved for further development.
研究领域:
药物化学
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肿瘤学
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分子生物学
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药物发现
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DOI
PubMed
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
·
2022
·Vol. 20
·期 28
·5535-5542
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IF 3.89
Na Li,Xiao Liu,Mingliang Zhang,Zekun Zhang,Beibei Zhang,Xiaohui Wang,Juan Wang,Pengfei Tu,Yong Jiang,She-po Shi
Prenyltransferases (PTs) play important roles in the biosynthesis and structural diversification of natural products. In the present study, two new PTs were characterized from a medicinal plant Murraya exotica. MePT1 unprecedentedly catalyses the formation of two C-geranylated products 8/6-C-geranylumbelliferone together with a trace product 7-O-geranylumbelliferone from umbelliferone. MePT2 regio-specifically catalyses the formation of C-3 dimethylallylated products from quinolone alkaloids. This is the first report that a plant PT catalyses the simultaneous formation of C- and O-prenylated products, and a plant PT specifically utilizes quinolone alkaloids as prenyl acceptors. The results not only provide important insight into the functional diversity of plant PTs and the biosynthesis of the prenylated coumarins, quinolone and carbazole alkaloids in Murraya plants, but also pave the way for the overproduction of the prenylated coumarins and alkaloids using metabolic engineering approaches.
研究领域:
生物化学
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植物生物技术
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生药学
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DOI
PubMed
高影响因子
TETRAHEDRON
·
2019
·
IF 2.379
Chongyang Zhao,Jian Chen,Duanlin Cao,Jianlong Wang,Wenbing Ma
In this study, we have successfully synthesized a novel coumarin-based dendrons derivative CD and its chemical structure was characterized by 1 H NMR, 13 C NMR and ESI-HR-MS. The sensor CD showed an obvious “on-off” fluorescence quenching response toward Cu 2+ with a maximum quenching efficiency of 99.8%. The CD -Cu 2+ complex showed an “off-on” fluorescence enhancement response toward PPi over many competitive anions. The detection limit of the sensor CD was 0.29 × 10 −6 M to Cu 2+ and 2.39 × 10 −9 M to PPi. In addition, the sensor CD showed a 1:1 binding stoichiometry to Cu 2+ and the sensor CD -Cu 2+ showed a 2:1 binding stoichiometry to PPi in CH 3 CN/HEPES buffer medium (9:1 v/v, pH = 7.2). The stable pH range of sensor CD to Cu 2+ and CD -Cu 2+ to PPi was from 3 to 8.
研究领域:
化学传感器
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分析化学
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DOI
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2018
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IF 3.185
Yu-Feng Shen,Lei Liu,Chen-Zhang Feng,Yang Hu,Cheng Chen,Gao-Xue Wang,Bin Zhu
Coumarin as a lead structure have received a considerable attention in the last three decades for the discovery of antiviral agents. Our previous study indicated that imidazole coumarins possessed antiviral activities against SVCV . Based on the structure-activity relationship in that study, a new imidazole coumarin derivative, 7-(4-benzimidazole-butoxy)-coumarin (BBC), was designed, synthesized and its anti-SVCV activity was evaluated. By comparing inhibitory concentration at half-maximal activity (IC 50 ), we found that BBC (IC 50 = 0.56 mg/L) possessed a higher antiviral activity than those imidazole coumarins in our previous study. Besides, BBC can significantly inhibit cell death and reduce cellular morphological damage induced by SVCV. Our further data indicated that intraperitoneal injection of BBC increased the survival rate of zebrafish by 17.5%, decreased viral titer in fish body and inhibited SVCV glycoprotein expression in kidney and spleen . In uninfected zebrafish, the expression levels of ifnγ , ifnφ1 , ifnφ2 and rig1 genes were up-regulated after BBC treatment, which indicated that BBC could activate interferon response. In addition, data of the antioxidant enzymes activities and results of the antioxidant enzymes-related genes expressions suggested BBC could reduce SVCV-induced oxidative damage in infected zebrafish. Altogether, BBC is expected to be a therapeutic agent against SVCV infection in the field of aquaculture.
研究领域:
水产养殖
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病毒学
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药理学
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产品关联
DOI
PubMed
高影响因子
Colloid and Interface Science Communications
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2021
·
IF 4.914
Weichun Wu,Shenxi Min,Qin Tong,Junhao Wang,Jianghong Hu,Ashish Dhamsaniya,Anamik K. Shah,Vaibhav P. Mehta,Bin Dong,Bo Song
As the third most abundant trace element in human internal environment, Cu 2+ has a significant impact on organisms and ecosystems. The determination of Cu 2+ is an important topic in the field of environmental protection and food safety. In this study, a coumarin-based fluorescent probe (denoted by ICTAB) was designed and synthesized. The results indicate that ICTAB is a “turn-off” fluorescent probe for Cu 2+ , with extremely high selectivity and sensitivity. The limit of detection is down to 0.27 μM. Mass spectroscopy and Job's plot show that ICTAB and Cu 2+ form 2:1 coordinate complexes, and the specific binding sites of Cu 2+ on ICTAB were determined by FTIR and 1 H NMR. More importantly, the fluorescent emission of ICTAB can be repeatedly recovered by removing Cu 2+ with S 2− , which functions as an effective “turn-off” fluorescent probe. ICTAB demonstrated over 89% of recoveries as being applied in detecting Cu 2+ in water.
研究领域:
分析化学
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环境科学
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食品安全
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产品关联
DOI
高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
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2021
·Vol. 28
·期 3
·e202103346
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IF 5.236
Zhongxian Fan,Jiaen Xie,Tumpa Sadhukhan,Chao Liang,Can Huang,Wenqing Li,Tingxuan Li,Pingyu Zhang,Samya Banerjee,Krishnan Raghavachari,Huaiyi Huang
Graphical Four novel Ir(III) photo-catalysts ( Ir1 – Ir4 ) were synthesized and applied for photocatalytic cancer therapy. Upon blue and green light irradiation, these photocatalysts generated singlet oxygen and induced rapid photo-catalytic oxidation of the cellular coenzymes NAD(P)H. Ir2 triggered promising photo-induced anticancer activity via induction of intracellular redox imbalance and exhibited ideal in vivo photo-induced catalytic anticancer activity. Four photo-catalysts of the general formula [Ir(CO6/ppy) 2 (L)]Cl where CO6=coumarin 6 ( Ir1 – Ir3 ), ppy=2-phenylpyridine ( Ir4 ), L=4′-(3,5-di-tert-butylphenyl)-2,2′ : 6′,2′′-terpyridine ( Ir1 ), 4′-(3,5-bis(trifluoromethyl)phenyl)-2,2′ : 6′,2′′-terpyridine ( Ir2 and Ir4 ), and 4-([2,2′ : 6′,2′′-terpyridin]-4′-yl)-N,N-dimethylaniline ( Ir3 ) were synthesized and characterized. These photostable photo-catalysts ( Ir1 – Ir3 ) showed strong visible light absorption between 400–550 nm. Upon light irradiation (465 and 525 nm), Ir1 – Ir3 generated singlet oxygen and induced rapidly photo-catalytic oxidation of cellular coenzymes NAD(P)H. Ir1 – Ir3 showed time-dependent cellular uptake with excellent intracellular retention efficiency. Upon green light irradiation (525 nm), Ir2 provided a much higher photo-index (PI=793) than the clinically used photosensitizer, 5-aminolevulinicacid (5-ALA, PI>30) against HeLa cancer cells. The observed necro-apoptotic anticancer activity of Ir2 was due to the Ir2 triggered photo-induced intracellular redox imbalance (by NAD(P)H oxidation and ROS generation) and change in the mitochondrial membrane potential. Remarkably, Ir2 showed in vivo photo-induced catalytic anticancer activity in mouse models.
研究领域:
癌症研究
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光化学
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Catalysts
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2022
·Vol. 12
·期 3
·339
·
IF 4.501
Li-Hua Du,Meng-Jie Yang,Yue Pan,Ling-Yan Zheng,Shi-Yi Zhang,Zhi-Kai Sheng,Ping-Feng Chen,Xi-Ping Luo
Coumarin carboxamide derivatives are important building blocks for organic synthesis and chemical biology due to their excellent biopharmaceutical properties. In this paper, we demonstrate for the first time a two-step enzymatic synthesis of coumarin carboxamide derivatives. Salicylaldehyde and dimethyl malonate were reacted to obtain coumarin carboxylate methyl derivatives, which were then reacted with various amines under the catalysis of lipase TL IM fromThermomyces lanuginosusto obtain coumarin carboxamide derivatives in continuous flow reactors. We studied various reaction parameters on the yields. The important features of this method include mild reaction conditions, a short reaction time (40 min), reduced environmental pollution, higher productivity (STY = 31.2941 g L−1h−1) and enzymes being relatively easy to obtain.Keywords:enzymatic synthesis;microreactor;coumarin carboxamide derivatives
研究领域:
有机化学
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生物催化
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药物化学
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产品关联
DOI
高影响因子
Journal of Food Measurement and Characterization
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2021
·Vol. 15
·期 6
·5439-5444
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IF 2.431
Fu Li,Chen Fei,Zhao Shichao,Yu Jinhong,Karimi-Maleh Hassan,Lin Cheng-Te
The detection of coumarins in real samples often requires a complex extraction process, which makes the analytical technique unable to meet the actual detection needs. In this work, we proposed a novel analytical technique based on the electrochemical reduction behavior of coumarins. This technique does not require complex pretreatment of the real sample, such as extraction and filtration. The sample particles were directly immobilized on the surface of the electrode after co-mixing with graphene. After a simple pre-reduction process, the amount of coumarin in the real sample can be evaluated by voltammetry. We have analyzed the feasibility of this technique by using cakes, fruits and different organ tissues of Glehnia littoralis . The results showed that this new analytical technique successfully achieved the rapid detection of coumarin content in real samples. The amount of coumarin in apples was 0.045 mg/g. The amount of coumarin in the roots, leaves and fruits of Glehnia littoralis was 0.037 mg/g, 0.011 mg/g and 0.079 mg/g, respectively.
研究领域:
分析化学
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食品科学
·
植物学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2018
·
IF 4.816
Hao Liu,Zi-Li Ren,Wei Wang,Jie-Xiu Gong,Ming-Jie Chu,Quan-Wei Ma,Jie-Chun Wang,Xian-Hai Lv
The identification of novel Topoisomerase II (Topo II) inhibitors is one of the most attractive directions in the field of bactericide research and development. In our ongoing efforts to pursue the class of inhibitors, six series of 70 novel coumarin-pyrazole carboxamide derivatives were designed and synthesized. As a result of the evaluation against four destructive bacteria, including Staphylococcus aureus , Listeria monocytogenes , Escherichia coli and Salmonella . Compound 8III-k (MIC = 0.25 mg/L) showed considerable inhibitory activity than ciprofloxacin (MIC = 0.5 mg/L) against Escherichia coli and 8V-c (MIC = 0.05 mg/L) exhibited excellent antibacterial activity than ciprofloxacin (MIC = 0.25 mg/L) against Salmonella . The selected compounds ( 8III-k , 8V-c and 8V-k ) exhibit potent inhibition against Topo II and Topo IV with IC 50 values (9.4–25 mg/L). Molecular docking model showed that the compounds 8V-c and 8V-k can bind well to the target by interacting with amino acid residues . It will provide some valuable information for the commercial Topo II inhibiting bactericides.
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DOI
PubMed
高影响因子
Expert Opinion on Drug Metabolism & Toxicology
·
2025
·
IF 3.4
Yongbin Tong,Qi Zhang,Yutong Chen,Zhiqiang Zhao,Jingqi Li,Jinyi Wang,Haishan Xia,Danyi Lu,Yuyu Liu
Introduction Coumarin exhibit various biological activities, including anti-inflammatory, antioxidant and anxiolytic effects. However, its clinical application is restricted due to significant hepatotoxicity observed in multiple animal models. CYP2A5 is the primary enzyme responsible for metabolizing coumarin in the mouse liver, homologous to human CYP2A6.Methods Acute toxicity and pharmacokinetic investigations were conducted on Rev-erbα−/− and wild-type mice following coumarin administration. The regulatory effects of REV-ERBα on CYP2A5 expression were assessed both in vivo and in vitro. Western blotting and qPCR were used to measure the protein and mRNA levels, respectively.Results Firstly, coumarin-induced hepatotoxicity was mitigated in Rev-erbα−/− mice. Secondly, the systemic exposure of coumarin was lowered in Rev-erbα−/− mice compared with wild-type mice. Thirdly, deletion of Rev-erbα resulted in significant upregulation of CYP2A5 mRNA and protein expression in mice. REV-ERBα negatively regulated CYP2A5/2A6 expression in Hepa-1c1c7 and HepG2 cells. Furthermore, luciferase reporter and chromatin immunoprecipitation (ChIP) assays indicated that REV-ERBα modulated Cyp2a5 transcription and expression through the repression of DBP.Conclusions The knockout of Rev-erbα significantly reduces the hepatotoxicity of coumarin by modulating CYP2A5. This research underscores the potential of targeting the REV-ERBα/CYP2A5 axis as a novel strategy for reducing coumarin-induced hepatotoxicity.
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产品关联
DOI
PubMed
高影响因子
TETRAHEDRON
·
2023
·
IF 2.1
Zifan Zhu,Xiaoqing Feng,Hecheng Wang,Jiaru Fan,Chen Zhang,Guoqiang Song,Long Tang
Coumarin and chalcone are two compounds that have been extensively studied for their neuroprotective effects. Coumarin is known for its ability to inhibit MAO activity in the brain and reduce central nervous system damage caused by dopamine degradation. Chalcone, on the other hand, has gained attention due to its potential medicinal value, including free radical scavenging, anti-inflammatory, and neuroprotective properties. Both compounds have shown promise in the development of treatments for neurodegenerative diseases like Alzheimer's disease . In this study, we designed and synthesized 36 coumarin-chalcone heteroderivatives based on the principle of structure hybridization . We then evaluated the inhibitory effects of these compounds on phosphodiesterase II (PDE2) at the enzyme level and analyzed their structure-activity relationship. Among the hybrid derivatives, compounds 2b , 3a , 3i , 3m , and 1l demonstrated significant inhibitory activity on PDE2, with IC50 values of 24.46 μM , 16.82 μM , 28.13 μM , 21.88 μM , and 29.72 μM , respectively. This paper presents the design, synthesis, and biological evaluation of coumarin-chalcone hybrid derivatives for their potential as PDE2 inhibitors.
研究领域:
药物化学
·
神经科学
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DOI
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 77
·49097-49101
·
IF 3.108
J. Huang,P. Liang,J. Xu,Y. Wu,W. Shen,B. Xu,D. Zhang,J. Xia,S. Zhuang
Coumarin is harmful to health but still used in cosmetics, tobacco, or illegally added into food as a spice in trace amounts so that it is exceedingly difficult to be determined accurately. Thus, it is important to develop a reliable method to qualitatively and quantitatively determine coumarin. Herein, we report a coumarin detection method using surface-enhanced Raman spectroscopy (SERS) coupled with an intelligent multivariate analysis. First, a flower-like silver-based substrate was fabricated and characterized by XRD, TEM, and EDS. Subsequently, coumarin with different concentrations was detected using this flower-like silver as the SERS substrate. The Raman vibration assignments reflect the information about the structure of the coumarin molecule efficiently. The limits of detection (LOD) for coumarin using the flower-like silver substrate can reach 10−8 M. It means the detection limit of coumarin by this method is less than 1.46 μg kg−1, which is much more sensitive than the previously reported one. Based on the Raman characteristic peaks of coumarin, various methods like linear regression, binary linear regression, and PCA were used to quantitatively analyze coumarin. These analysis results show that with the binary linear regression model, a strong linear relationship between lg I (I is the Raman peak intensity) and −lg C (C is the concentration of coumarin) can be observed and the correlation coefficient R2 was close to 1. This method provides a high sensitivity and rapid method to detect the additives in food and cosmetics, etc.
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DOI
高影响因子
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