- Hafnium chloride tetrahydrofuran complex-catalyzed Diels-Alder cycloadditions of 3-ethoxycarbonylcoumarins with 1,3-dienes under solvent-free conditions
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Hafnium chloride tetrahydrofuran complex (HfCl4·2 THF) is an efficient catalyst for the Diels-Alder cycloadditions of 3-ethoxycarbonylcoumarins 1a-c and 1,3-butadienes 2x-z under solvent-free conditions furnishing the corresponding cycloadducts in excellent yields. This salt is an air stable Lewis acid and therefore the reactions can be performed in air atmosphere making the procedure simple to be carried out.
- Fringuelli, Francesco,Girotti, Rugiada,Pizzo, Ferdinando,Zunino, Ennio,Vaccaro, Luigi
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- Design, synthesis and anti-Alzheimer's activity of novel 1,2,3-triazole-chromenone carboxamide derivatives
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Alzheimer's disease (AD) is a well-known neurodegenerative disorder affecting millions of old people worldwide and the corresponding epidemiological data highlights the significance of the disease. As AD is a multifactorial illness, various single-target directed drugs that have reached clinical trials have failed. Therefore, various factors associated with outset of AD have been considered in targeted drug discovery and development. In this work, a wide range of 1,2,3-triazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase inhibitory activity. Among them, N-(1-benzylpiperidin-4-yl)-7-((1-(3,4-dimethylbenzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-oxo-2H-chromene-3-carboxamide (11b) showed the best acetylcholinesterase inhibitory activity (IC50 = 1.80 μM), however, it was inactive toward butyrylcholinesterase. It should be noted that compound 11b was evaluated for its BACE1 inhibitory activity and calculated IC50 = 21.13 μM confirmed desired inhibitory activity. Also, this compound revealed satisfactory neuroprotective effect against H2O2-induced cell death in PC12 neurons at 50 μM as well as metal chelating ability toward Fe2+, Cu2+, and Zn2+ ions.
- Rastegari, Arezoo,Nadri, Hamid,Mahdavi, Mohammad,Moradi, Alireza,Mirfazli, Seyedeh Sara,Edraki, Najmeh,Moghadam, Farshad Homayouni,Larijani, Bagher,Akbarzadeh, Tahmineh,Saeedi, Mina
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- Synthesis and structural characterization of some divalent metal complexes: DNA binding and antitumor activity
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New Complexes (1–4) of Cu(II), Ni(II) Zn(II) and Mn(II) with 3-Ethoxy-6-(phenyl azo)-7-hydroxy coumarin (HL) have been prepared and characterized by elemental analyses, IR, 1H NMR, 13C NMR, mass spectroscopy and UV–Visible spectra as well as thermal measurements. IR spectra showed that the ligand (HL) acts as a monobasic bidentate and coordinating via the nitrogen atom of the azo group ([sbnd]N[dbnd]N[sbnd]) and oxygen atom of the deprotonated phenolic OH group. The molar conductance measurements proved that all the complexes are non-electrolytes. Also the important fragments in the ligand and Ni(II) complex were done using mass spectra and the main peaks were corresponding to the molecular weights. The molecular and electronic structures of the investigated compounds were also studied using quantum chemical calculations. The bonding parameters of the complexes have been calculated. Molecular docking was used to predict the binding between azo compound with the receptor of 3hb5-oxidoreductase receptor of breast cancer and of 2q7k-hormone of prostate cancer. The calf thymus DNA binding activity of the ligand and its metal complexes was studied by absorption spectra and viscosity measurement. The antitumor activity of the ligand and its metal complexes was tested against human cancer MCV-7 (breast cancer).
- El-Bindary, Ashraf El Bindary,Hassan,El-Afify
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- Coumarin-derived Fe3+-selective fluorescent turn-off chemosensors: Synthesis, properties, and applications in living cells
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A novel coumarin-based fluorogenic probe bearing the tris unit (DAT-1) with high selectivity and suitable affinity toward Fe3+ over other cations tested was developed in biological systems. The sensing mechanism was studied by quantum calculations. The probe can be applied to the monitoring of Fe3+ in aqueous solution with a pH span of 3-8. In addition, biological imaging, membrane permeability and nontoxicity demonstrate that DAT-1 could act as a turn-off fluorescent chemosensor for Fe3+ in living cells.
- En, Da,Guo, Yuan,Chen, Bo-Ting,Dong, Biao,Peng, Meng-Jiao
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- 7-Alkoxy-appended coumarin derivatives: synthesis, photo-physical properties, aggregation behaviours and current-voltage (I-V) characteristic studies on thin films
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In this study, we designed and synthesised a series of coumarin derivatives appended with a long alkoxy chain on the seventh position of the coumarin-3-carboxylate/carboxylic acid core to make thin film materials. Synthesised compounds were characterized by their UV and fluorescence spectra in solutions as well as their films prepared by both LB and spin-coated methods. The surface morphology and electrical behaviour of thin films were judged by AFM, SEM andI-Vcharacteristic mapping respectively. Isotherm, UV-Vis absorption and fluorescence spectroscopic investigations revealed the formation of aggregates on thin films. The result of SEM and AFM images provides the information about the length and height of aggregates on the thin films of coumarin derivatives. FromI-Vcharacteristics, it was found that at room temperature, the spin-coated films of coumarin derivatives containing an ester functional group exhibited a threshold switching behaviour, whereas derivatives containing the carboxylic acid functional group showed both threshold and bipolar switching behaviours. We also noticed that theI-Vcharacteristic features of synthesized materials depended on the length of the alkyl chain of individual series.
- Rudra Paul, Abhijit,Dey, Bapi,Suklabaidya, Sudip,Hussain, Syed Arshad,Majumdar, Swapan
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- A sustainable innovation for the tandem synthesis of sugar-containing coumarin derivatives catalyzed by lipozyme TL im from: Thermomyces lanuginosus in continuous-flow microreactors
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We developed an efficient and environmentally friendly two-step tandem methodology for the synthesis of sugar-containing coumarin derivatives catalyzed by lipozyme TL IM from Thermomyces lanuginosus in continuous-flow microreactors. Compared to those observed for other methods, the salient features of this work including green reaction conditions, short residence time (50 min), and catalysts are more readily available and the biocatalysis reaction process is efficient and easy to control. This two-step tandem synthesis of coumarin derivatives using the continuous-flow technology is a proof of concept that opens the use of enzymatic microreactors in coumarin derivative biotransformations.
- Chen, Ping-Feng,Du, Li-Hua,Long, Rui-Jie,Luo, Xi-Ping,Xue, Miao
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- Selective and "turn-off" fluorimetric detection of mercury(II) based on coumarinyldithiolane and coumarinyldithiane in aqueous solution
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In this work, five novel coumarin-based fluorescent probes for mercury ions were developed. The recognition of mercury ions was performed via the mercury(II)-promoted desulfurization of the probes and a reasonable reaction mechanism was proposed and verified by thin layer chromatography (TLC), 1H nuclear magnetic resonance (1H NMR) and fluorescence intensity measurements. All the probes showed excellent optical properties and exclusively distinguish mercury ions from various metal ions in aqueous solutions at pH 7.4. The linear response of the fluorescence emission intensity for all the probes to the concentration of mercury ions was obtained over a wide range of 0.06-1.5 μM (0.06-0.9 μM for probe 3e). In addition, the biological toxicity and the confocal fluorescence images of probe 3a were also tested on MCF-7 cells.
- Guo, Yuan,An, Jing,Tang, Haoyang,Peng, Mengjiao,Suzenet, Franck
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- Ratiometric assay of CARM1 activity using a FRET-based fluorescent probe
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One of the regulatory mechanisms of epigenetic gene expression is the post-translational methylation of arginine residues, which is catalyzed by protein arginine methyltransferases (PRMTs). Abnormal expression of PRMT4/CARM1, one of the PRMTs, is associated with various diseases, including cancers. Here, we designed and synthesized a F?rster resonance energy transfer (FRET)-based probe, FRC, which contains coumarin and fluorescein fluorophores at the N-terminus and C-terminus of a peptide containing an arginine residue within an appropriate amino acid sequence to serve as a substrate of CARM1; the two fluorophores act as a FRET donor and a FRET acceptor, respectively. Since trypsin specifically hydrolyzes the arginine residue, but not a monomethylarginine or dimethylarginine residue, CARM1 activity can be evaluated from the change of the coumarin/fluorescein fluorescence ratio of FRC in the presence of trypsin.
- Ohta, Yuhei,Wakita, Hiroo,Kawaguchi, Mitsuyasu,Ieda, Naoya,Osada, Shigehiro,Nakagawa, Hidehiko
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- Discovery of quinazoline-based fluorescent probes to α1-adrenergic receptors
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α1-Adrenergic receptors (α1-ARs), as the essential members of G protein-coupled receptors (GPCRs), can mediate numerous physiological responses in the sympathetic nervous system. In the current research, a series of quinazoline-based small-molecule fluorescent probes to α1-ARs (1a-1e), including two parts, a pharmacophore for α1-AR recognition and a fluorophore for visualization, were well designed and synthesized. The biological evaluation results displayed that these probes held reasonable fluorescent properties, high affinity, accepted cell toxicity, and excellent subcellular localization imaging potential for α1-ARs.
- Zhang, Wei,Ma, Zhao,Li, Wenhua,Li, Geng,Chen, Laizhong,Liu, Zhenzhen,Du, Lupei,Li, Minyong
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- A coumarin-based fluorescent probe for the fast detection of Pd0 with low detection limit
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A off-on coumarin-based fluorescent probe for the fast detection of Pd0 is designed and synthesized. The probe shows not only good selectivity but also fast response to Pd0 in phosphate buffered saline (PBS) solution. The absorption band at 412 nm rises sharply as well as the fluorescence at 450 nm after the addition of Pd0 within few minutes. The detection limit is as low as 0.34 nM. The probe shows nonfluorescence when it conjuncted with allyl carbonate ester which destroys the Intramolecular Charge Transfer (ICT) system. The effect of Pd0 to the probe can change the structure and make the departure of the conjuncted allyl carbonate ester. As a result, the fluorogen is exposed and it shows fluorescence.
- Liu, Yunchang,Xiang, Kaiqiang,Guo, Min,Tian, Baozhu,Zhang, Jinlong
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- A simple and sensitive fluorescent probe for specific detection of cysteine
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Abstract: A fluorescent probe, with simplicity of structure and convenience of synthesis, is capable of detecting cysteine over other biothiols, such as homocysteine and glutathione. The detection limit of 60?nM and 190-fold increase in fluorescence intensity offer advantage for detection of Cys in biological systems. Furthermore, the probe 1 could be applied in bioimaging. Graphical abstract: We designed and synthesized the fluorescent probe 1, which displayed a highly selective and sensitive response to Cys over Hcy/GSH. The detection limit of 60?nM and 190-fold increase in fluorescence intensity offer advantage for detection of Cys in biological systems. Furthermore, the probe 1 could be applied in bioimaging. [Figure not available: see fulltext.].
- Kang, Yan-Fei,Qiao, Hai-Xia,Meng, Ya-Li,Xin, Zhen-Hui,Ge, Li-Ping,Zheng, Jin-Nan,Wang, Yi-Na
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- A novel fluorescent probe for hydrogen peroxide and its application in bio-imaging
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Hydrogen peroxide (H2O2) plays an important role in the human body and monitoring its level is meaningful due to the relationship between its level and diseases. A fluorescent sensor (CMB) based on coumarin was designed and its ability for detecting hydrogen peroxide by fluorescence signals was also studied. The CMB showed an approximate 25-fold fluorescence enhancement after adding H2O2 due to the interaction between the CMB and H2O2 and had the potential for detecting physiological H2O2. It also showed good biocompatibility and permeability, allowing it to penetrate cell membranes and zebrafish tissues, thus it can perform fluorescence imaging of H2O2 in living cells and zebrafish. This probe is a promising tool for monitoring the level of H2O2in related physiological and pathological research.
- Duan, Chunying,Jiao, Yang,Ma, Chunming,Zuo, Yingying
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- A FRET-ICT dual-quenching fluorescent probe with large off-on response for H2S: Synthesis, spectra and bioimaging
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A FRET-ICT dual-quenching probe with large off-on fluorescent response upon H2S treatment is reported. The probe can be used for bioimaging of endogenous H2S in living cells. This journal is
- Zhang, Changyu,Wei, Lv,Wei, Chao,Zhang, Jie,Wang, Runyu,Xi, Zhen,Yi, Long
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- Synthesis and Cytotoxicity Against Human Breast Carcinoma Cell Evaluation of Some New 3,4-Disubstituted Coumarin Derivatives
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A novel series of 3,4-disubstitutued coumarin derivatives have been synthesized by the reaction of ethyl coumarin-3-carboxylate with pyrazole-3,5-dione and condensation of ethyl 7-hydroxycoumarin-3-carboxylate with 4,6-dibromo-3-amino phenol. Acylation with acetic anhydride and condensation of coumarin derivatives with 2-hydroxybenzaldehyde yielded the corresponding acetyl derivatives and 4-substituted pyrazole derivatives. Structures of the synthesized compounds were elucidated by spectral methods and elemental analysis. All the prepared derivatives were evaluated for their cytotoxicity against human breast carcinoma cell line (MCF-7). Compound VI showed the least IC50 value in MTT colorimetric assay as compared to that of the standard marketed drug staurosporin.
- Radwan, Eman M.,Elsayed, Elsherbiny H.,El-Moneim, Mohamed Abd,Youssef Moustafa, Amal M.
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p. 1040 - 1049
(2022/01/11)
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- NO Donor coumarin furoxan conjugates and pharmaceutical use thereof
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The invention belongs to the technical field of chemical pharmacy. Experiments prove that the furoxan conjugate has good water 3 - solubility, has excellent inhibitory activity on the growth of sensitive human tumor cells and resistant tumor cells, and NO
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Paragraph 0114-0116
(2021/10/13)
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- Structure-Activity Relationship Studies of Coumarin-like Diacid Derivatives as Human G Protein-Coupled Receptor-35 (hGPR35) Agonists and a Consequent New Design Principle
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A series of coumarin-like diacid derivatives were designed and synthesized as novel agonists of human G-protein-coupled receptor 35 (hGPR35). Active compounds were characterized to possess one acidic group on both sides of a fused tricyclic aromatic scaff
- Wei, Lai,Hou, Tao,Li, Jiaqi,Zhang, Xiuli,Zhou, Han,Wang, Zhenyu,Cheng, Junxiang,Xiang, Kaijing,Wang, Jixia,Zhao, Yaopeng,Liang, Xinmiao
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supporting information
p. 2634 - 2647
(2021/04/02)
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- Synthesis and anticancer activity of new coumarin-3-carboxylic acid derivatives as potential lactate transport inhibitors
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As an oncometabolite, lactate plays a very important role in tumor proliferation, metastasis, angiogenesis, immune escape and other tumor biological functions. Pharmacological inhibition of lactate transport has been viewed as a promising therapeutic strategy to target a range of human cancers. In this study, a series of new coumarin-3-carboxylic acid derivatives 5a-t and 9a-b were synthesized and evaluated as lactate transport inhibitors. Their cytotoxic activity has been tested against three cell lines high-expressing and low-expressing monocarboxylate transporter 1 (MCT1) which acts as the main carrier for lactate. Compound 5c-e, 5g-i and 5m-o showed significant cytotoxicity and good selectivity against Hela and HCT116 cell lines with high MCT1 expression. Notably, coumarin-3-hydrazide 5o, the lead molecule with the most potent cytotoxic activity, exhibited significant anti-proliferation and apoptosis induction effects. Further studies revealed that compound 5o decreased the expression level of target MCT1, and suppressed the energetic metabolism of Hela and HCT116 cells by remarkably reducing glucose consumption and lactate production. Additionally, compound 5o induced intracellular lactate accumulation and inhibited lactate uptake, which implied that it blocked lactate transport via MCT1. These results indicate a good start point for the development of lactate transport inhibitors as new anticancer agents.
- Ji, Hong,Tan, Yaling,Gan, Nana,Zhang, Jing,Li, Shannuo,Zheng, Xuan,Wang, Zhaohua,Yi, Wei
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supporting information
(2020/12/02)
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- Design, Synthesis, and Anti-Breast Cancer Activity of Some Hybrid Molecules Containing Coumarin Moiety
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Abstract: (Benzimidazol-2-yl)-7-hydroxycoumarin and N-(2-hydroxyphenyl)-7-hydroxycoumarin-3-carboxamide have been synthesized by the condensation of ethyl 7-hydroxycoumarin-3-carboxylate in acetic acid. Acetylation with acetic anhydride and halogenation w
- Eman M. Radwan,Elsayed, Elsherbiny H.,El-Moneim, Mohamed Abd,Moustafa, Amal M. Youssef
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p. 149 - 157
(2021/04/05)
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- Synthesis and Biological Evaluation of Some New 3,4-Disubstituted Coumarin Derivatives as Anticancer Agents
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A new series of 3, 4-disubstitutued coumarin derivatives have been synthesized by the reaction of ethyl coumarin-3-carboxylate with pyrazole-3,5-dione and condensation of ethyl 7-hydroxycoumarin-3-carboxylate with 4,6-dibromo-3-amino phenol. Acylation with acetic anhydride and condensation of coumarin derivatives with 2-hydroxybenzaldehyde yielded the corresponding acetyl derivatives and 4-substituted pyrazole derivatives. The structure of the synthesized compounds was elucidated using spectral and elemental analysis. All the prepared derivatives were evaluated for their cytotoxicity against human breast carcinoma cell line (MCF-7). Compound VI has shown the least IC50 values in dimethylthiazol-diphenyltetrazolium bromide colorimetric assay compared with that of the standard marketed drug, staurosporine drug.
- El-Moneim Mahmoud Mohamed, Mohamed Abd,El-Sayed Yuossif, El-Sherbiny Hamdy,Mahmoud Radwan, Eman Mossad,Youssef Moustafa, Amal Mahmoud
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p. 101 - 111
(2021/08/12)
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- A coumarin-based portable fluorescent probe for rapid turn-on detection of amine vapors
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Amines are widely used in many fields including agriculture, dyes, medicine and food processing. However, volatile amine vapors could initiate acute and serious damage to human bodies. Thus, highly efficient detection of volatile amine vapors has great importance for academic research as well as practical application. In this work, a turn-on type fluorescent sensor BZCO has been developed, which could be used to detect volatile amine vapors. The portable BZCO sensor can be easily prepared through immersing filter paper into its CH2Cl2 solution and then evaporating it to dryness. This paper-based amine vapor sensor exhibits high sensitivity with a relatively low detection limit at 3.82 ppm. It also has good selectivity for discriminating amine vapors from volatile organic solvents. The detection mechanism has been confirmed by UV–vis spectral analysis. The practical applications of this paper-based BZCO sensor, such as detection of food spoilage and fluorescent security ink, have been investigated. This work has developed a new fluorescent sensor BZCO, which has broad applications in various fields, including amine gas detection, security and anti-counterfeiting materials.
- Chen, Shaojin,Du, Chunhui,Hu, Zhi-Qiang,Jia, Ke,Liu, Chunfang,Meng, Yuanyuan,Wang, Kun-Peng,Yuan, Chunming
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- 2H - furo [GPR35, 2] chromene derivatives as 3 - H receptor agonists. Preparation method and application
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The invention provides 2H - furo [GPR35, 2] chromene derivatives as 3 - H receptor agonists, a preparation method and an application thereof. Such compounds generally exhibit agonistic activity against human GPR35 receptors and are specific agonists of hu
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Paragraph 0047; 0054-0055
(2021/10/13)
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- Thiolysis of CBD arylethers for development of highly GSH-selective fluorescent probes
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Thiolysis of 7-cyanobenzoxadiazole (CBD) arylether was investigated for development of GSH-selective fluorescent probes for the first time. The results demonstrate that CBD-based probes have tunable reactivities and appropriate dissociation constants for
- Tu, Xiaoqiang,He, Lijun,Huang, Haojie,Ye, Haishun,Sun, Lu,Yi, Long
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supporting information
p. 8802 - 8805
(2021/09/07)
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- Site-specific fluorogenic protein labelling agent for bioconjugation
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Many clinically relevant therapeutic agents are formed from the conjugation of small molecules to biomolecules through conjugating linkers. In this study, two novel conjugating linkers were prepared, comprising a central coumarin core, functionalized with a dimaleimide moiety at one end and a terminal alkyne at the other. In our first design, we developed a protein labelling method that site-specifically introduces an alkyne functional group to a dicysteine target peptide tag that was genetically fused to a protein of interest. This method allows for the subsequent attachment of azide-functionalized cargo in the facile synthesis of novel protein-cargo conjugates. However, the fluorogenic aspect of the reaction between the linker and the target peptide was less than we desired. To address this shortcoming, a second linker reagent was prepared. This new design also allowed for the site-specific introduction of an alkyne functional group onto the target peptide, but in a highly fluorogenic and rapid manner. The site-specific addition of an alkyne group to a protein of interest was thus monitored in situ by fluorescence increase, prior to the attachment of azide-functionalized cargo. Finally, we also demonstrated that the cargo can also be attached first, in an azide/alkyne cycloaddition reaction, prior to fluorogenic conjugation with the target peptide-fused protein.
- Keillor, Jeffrey W.,Lee, Ann C.,Racine, Karl é.,Tsao, Kelvin K.
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- Preparation and application of novel fluorescent probe and test paper for hydrazine hydrate detection
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The invention relates to preparation and application of a novel fluorescent probe and test paper for hydrazine hydrate detection, and belongs to the technical field of analytical chemistry. The fluorescent probe takes a benzothiazole mother nucleus as a parent and acetyl as a recognition site, and the chemical structure of the fluorescent probe is shown as a formula (I). When the fluorescent probereacts with hydrazine hydrate, acetyl is hydrolyzed into hydroxyl, a fluorescent substance with high fluorescence emission capacity is generated in a PBS-CH3CN (10 mM, 3: 7, v/v, pH=7.4) buffer solution, fluorescence is changed from blue to green, and ratio type detection of hydrazine hydrate is realized. Besides, the fluorescent probe only responds to hydrazine hydrate, does not respond to smallmolecules such as methylamine, ethylamine, ethylenediamine, butylamine, dodecylamine, n-hexylamine, octadecylamine, aniline, Cys and GSH, and can realize specific recognition of hydrazine hydrate. Inaddition, the fluorescent probe provided by the invention can also be used for rapid detection of hydrazine hydrate in the environment, and has a very good application prospect. Formula I is shown.
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Paragraph 0023
(2020/12/31)
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- Rational design, synthesis and biological evaluation of novel multitargeting anti-AD iron chelators with potent MAO-B inhibitory and antioxidant activity
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A series of (3-hydroxypyridin-4-one)-coumarin hybrids were developed and investigated as potential multitargeting candidates for the treatment of Alzheimer's disease (AD) through the incorporation of iron-chelating and monoamine oxidase B (MAO-B) inhibition. This combination endowed the hybrids with good capacity to inhibit MAO-B as well as excellent iron-chelating effects. The pFe3+ values of the compounds were ranging from 16.91 to 20.16, comparable to more potent than the reference drug deferiprone (DFP). Among them, compound 18d exhibited the most promising activity against MAO-B, with an IC50 value of 87.9 nM. Moreover, compound 18d exerted favorable antioxidant activity, significantly reversed the amyloid-β1-42 (Aβ1-42) induced PC12 cell damage. More importantly, 18d remarkably ameliorated the cognitive dysfunction in a scopolamine-induced mice AD model. In brief, a series of hybrids with potential anti-AD effect were successfully obtained, indicating that the design of iron chelators with MAO-B inhibitory and antioxidant activities is an attractive strategy against AD progression.
- Bai, Renren,Gu, Jinping,Guo, Jianan,Jiang, Xiaoying,Lv, Yangjing,Mi, Zhisheng,Shi, Yuan,Xie, Yuanyuan,Yao, Chuansheng,Zhang, Changjun,Zhou, Tao
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- 7-Hydroxycoumarins Are Affinity-Based Fluorescent Probes for Competitive Binding Studies of Macrophage Migration Inhibitory Factor
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Macrophage migration inhibitory factor (MIF) is a cytokine with key roles in inflammation and cancer, which qualifies it as a potential drug target. Apart from its cytokine activity, MIF also harbors enzyme activity for keto-enol tautomerization. MIF enzymatic activity has been used for identification of MIF binding molecules that also interfere with its biological activity. However, MIF tautomerase activity assays are troubled by irregularities, thus creating a need for alternative methods. In this study, we identified a 7-hydroxycoumarin fluorophore with high affinity for the MIF tautomerase active site (Ki = 18 ± 1 nM) that binds with concomitant quenching of its fluorescence. This property enabled development of a novel competition-based assay format to quantify MIF binding. We also demonstrated that the 7-hydroxycoumarin fluorophore interfered with the MIF-CD74 interaction and inhibited proliferation of A549 cells. Thus, we provide a high-affinity MIF binder as a novel tool to advance MIF-oriented research.
- Xiao, Zhangping,Chen, Deng,Song, Shanshan,Van Der Vlag, Ramon,Van Der Wouden, Petra E.,Van Merkerk, Ronald,Cool, Robbert H.,Hirsch, Anna K. H.,Melgert, Barbro N.,Quax, Wim J.,Poelarends, Gerrit J.,Dekker, Frank J.
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p. 11920 - 11933
(2020/11/26)
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- Preparation method of organic-inorganic hybrid perovskite material with good stability in water
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The invention discloses a preparation method of an organic-inorganic hybrid perovskite material with good stability in water, and belongs to the technical field of biological materials. The preparation method comprises the following process steps: step 1, synthesizing and preparing a DAT probe molecule; 2, adding a DAT ligand into CsPbBr3 prepared by a thermal injection method, and carrying out heating reflux for 24 hours in DMF (Dimethyl Formamide) in an environment of 100-180 DEG C to form an organic fluorescent sensing material; step 3, preparing a standard solution with a concentration of1 [mu] mol/ml by using the prepared organic-inorganic hybrid perovskite material, adding 100 [mu] l of the standard solution into each centrifuge tube, then adding 100 [mu] l of cyclohexane, and thenadding 100 [mu] l of water and 100 [mu] l of a buffer solution; step 4, respectively adding 100 [mu] l of Fe ion standard solutions with different concentrations into the solution through ultrasonic treatment; and step 5, sequentially carrying out spectral analysis on the mixed solutions, and finally drawing a detection limit diagram; the water stability is improved; and meanwhile, the organic-inorganic hybrid perovskite material has the advantages of a fluorescence detection reagent.
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Paragraph 0008; 0031; 0032
(2020/05/08)
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- Design, synthesis and biological evaluation of coumarin-based N-hydroxycinnamamide derivatives as novel histone deacetylase inhibitors with anticancer activities
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A series of novel coumarin-based N-hydroxycinnamamide derivatives were designed and synthesized as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds showed potent HDAC inhibitory activity and significant antiproliferative activity a
- Cheng, Maojun,Ding, Jiaoli,Fang, Yuanying,Guan, Zhiyu,Guo, Jie,Jin, Yi,Liu, Jing,Wan, Yang,Wang, Rikang,Xie, Sai-Sai,Zhang, Zhipeng
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- Coumarin derivatives as well as preparation method and application thereof
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The invention discloses a coumarin derivative shown as a general formula A, B or C and a preparation method of the coumarin derivative. The compound shows agonistic activity on a G protein coupled receptor 35 (GPR35), and is a specific agonist of the GPR3
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Paragraph 0119-0122
(2020/07/24)
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- Design, synthesis and biological evaluation of coumarin-3-carboxamides as selective carbonic anhydrase IX and XII inhibitors
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A series of novel 7-hydroxycoumarin-3-carboxamides was synthesized by the reaction of 7-hydroxy-2-oxo-2H-chromene-3-carboxylic acid with various substituted aromatic amines. The newly synthesized compounds were evaluated for their inhibitory activity against the four physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms CA I, CA II, CA IX and CA XII. The CA inhibition results show that the newly synthesized 7-hydroxycoumarin-3-carboxamides (4a-n) exhibited selective inhibition of the tumor associated isoforms, CA IX and CA XII over CA I and II isoforms. The inhibition constants ranged from sub micromolar to low micromolar. Amongst all the compounds tested, compound 4m was the most effective inhibitor exhibiting sub micromolar potency against both hCA IX and hCA XII, with a Ki of 0.2 μM. Therefore, it can be anticipated that compound 4m can serve as a lead for development of anticancer therapy by exhibiting a novel mechanism of action. The binding modes of the most potent compounds within hCA IX and XII catalytic clefts were investigated by docking studies.
- Thacker, Pavitra S.,Alvala, Mallika,Arifuddin, Mohammed,Angeli, Andrea,Supuran, Claudiu T.
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p. 386 - 392
(2019/02/15)
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- Synthetic Fluorogenic Peptides Reveal Dynamic Substrate Specificity of Depalmitoylases
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Palmitoylation is a post-translational modification involving the thioesterification of cysteine residues with a 16-carbon-saturated fatty acid. Little is known about rates of depalmitoylation or the parameters that dictate these rates. Here we report a modular strategy to synthesize quenched fluorogenic substrates for the specific detection of depalmitoylase activity and for mapping the substrate specificity of individual depalmitoylases. We demonstrate that human depalmitoylases APT1 and APT2, and TgPPT1 from the parasite Toxoplasma gondii, have distinct specificities that depend on amino acid residues distal to the palmitoyl cysteine. This information informs the design of optimal and non-optimal substrates as well as isoform-selective substrates to detect the activity of a specific depalmitoylase in complex proteomes. In addition to providing tools for studying depalmitoylases, our findings identify a previously unrecognized mechanism for regulating steady-state levels of distinct palmitoylation sites by sequence-dependent control of depalmitoylation rates. Amara et al. describe a method for preparing positional scanning libraries of fluorogenic palmitoylated peptide substrates. This allowed identification of residues that are distal to the palmitoylation site that impact turnover. This information allowed the design of substrates that are selective for a specific depalmitoylating enzyme.
- Amara, Neri,Foe, Ian T.,Onguka, Ouma,Garland, Megan,Bogyo, Matthew
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p. 35 - 7,47
(2018/10/24)
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- Antifungal activity, mode of action variability, and subcellular distribution of coumarin-based antifungal azoles
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Azole antifungals inhibit the biosynthesis of ergosterol, the fungal equivalent of cholesterol in mammalian cells. Here we report an investigation of the activity of coumarin-substituted azole antifungals. Screening against a panel of Candida pathogens, including a mutant lacking CYP51, the target of antifungal azoles, revealed that this enzyme is inhibited by triazole-based antifungals, whereas imidazole-based derivatives have more than one mode of action. The imidazole-bearing antifungals more effectively reduced trailing growth associated with persistence and/or recurrence of fungal infections than triazole-based derivatives. The imidazole derivatives were more toxic to mammalian cells and more potently inhibited the activity of CYP3A4, which is one of the main causes of azole toxicity. Using live cell imaging, we showed that regardless of the type of azole ring fluorescent 7-diethylaminocoumarin-based azoles localized to the endoplasmic reticulum, the organelle that harbors CYP51. This study suggests that the coumarin is a promising scaffold for development of novel azole-based antifungals that effectively localize to the fungal cell endoplasmic reticulum.
- Elias, Rebecca,Benhamou, Raphael I.,Jaber, Qais Z.,Dorot, Orly,Zada, Sivan Louzoun,Oved,Pichinuk, Edward,Fridman
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supporting information
p. 779 - 790
(2019/07/10)
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- Synthesis and Spectroscopic Characterization of Some Hydrazone and 2H-benzopyranone Derivatives as Antitumor Agents
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A new series of hydrazone, 2H-benzopyranone-3-carboxamide and 2H-benzopyranone-3-carbonylthiosemicarbazide derivatives were synthesized from the alkyl 7-hydroxy-2H-benzopyranone-3-carboxylate (1a,b) and dibromo derivatives (6a,b) as a key starting materia
- Abumelha, Hana M.?A.
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p. 1738 - 1745
(2018/07/25)
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- Effect of conformational flexibility on photophysics of bis-coumarins
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The fluorescence intensity of bis-coumarins linked via CONH and COO functionalities are shown to exhibit a strong dependance on solvent polarity. The presence of the intramolecular hydrogen bond between the CO oxygen atom of coumarin and amide-NH moieties reduces the number of thermodynamically populated conformations in both ground and electronically excited states and an anti-arrangement of coumarin units is favored. Additionally, the rigidity of the linker raises the barrier to the conical intersection with the ground state, and in non-polar solvents strong fluorescence is observed. Although changing the CONH linking position from 3-7′ to 3-6′, does not remarkably affect the photophysics, replacement with a flexible ester linker allows the molecule a greater degree of conformational freedom due to the absence of the intramolecular hydrogen bonding interaction. The photophysical effect of this is the appearance of two fluorescence bands, the relative intensity and spectral positions of which are sensitive to the environment. Theoretical explorations of the excited-state potential energy surfaces performed with the aid of the ADC(2) ab initio electronic structure theory method revealed an exceptional wealth of concomitant photophysical processes. In particular, two channels for radiationless deactivation of the excited state were found; the first is related to the inter-ring twist of the coumarin units, and the second is associated with the excited-state intramolecular proton-transfer (ESIPT) from the CONH linker to the coumarin core.
- Kielesiński, ?ukasz,Gryko, Daniel T.,Sobolewski, Andrzej L.,Morawski, Olaf W.
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p. 14491 - 14503
(2018/06/08)
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- Novel probes based on coumarin-bisdithiocarbamate system for selective recognition of Ag(I) in aqueous solution
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Two novel fluorescent probes (C1, C2), comprising a coumarin moiety as fluorophore and a pair of dithiocarbamates as recognition sites, were designed and synthesized as fluorescent probes for Ag+. The probes exhibited high selectivity for Ag+ with fluorescence enhancement (FE) in CH3CN/4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) (1:9, v/v, pH 7.38); the selectivity was not affected by other metal ions. The binding ratio of C2–Ag+ complex was determined to be 1:1 according to the Job plot and mass spectroscopy (MS) data. The association constant Ka of Ag+ with C2 was 1.6?×?104?M?1. These probes could be applied for monitoring of Ag+ in aqueous solution in the pH range of 5.0–8.0, with calculated detection limit of 0.27?μM.
- Chen, Guo Feng,Liu, Lin,Wu, Jiu Li,Wu, Suo Juan,Chen, Bao Hua
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p. 1381 - 1395
(2017/11/16)
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- Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents
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To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids. The results had shown that these derivatives obviously inhibited proliferation of HT-29 cell lines, arrested G0/G1 phase of HT-29 cells, suppressed the migration of tumor cells, and induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells. Interestingly, the hybrids also induced the other cell death pathway-ferroptosis.
- Yu, Haonan,Hou, Zhuang,Tian, Ye,Mou, Yanhua,Guo, Chun
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p. 434 - 449
(2018/04/14)
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- Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer's disease based on coumarin and lipoic acid scaffolds
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A novel series of coumarin-lipoic acid conjugates were synthesized via cycloaddition click reaction to find out new multi-target-directed ligands (MTDLs) for treatment of Alzheimer's disease (AD). All of synthesized compounds were screened for neuroprotec
- Jalili-Baleh, Leili,Forootanfar, Hamid,Kü?ükk?l?n?, Tuba Tüylü,Nadri, Hamid,Abdolahi, Zahra,Ameri, Alieh,Jafari, Mandana,Ayazgok, Beyza,Baeeri, Maryam,Rahimifard, Mahban,Abbas Bukhari, Syed Nasir,Abdollahi, Mohammad,Ganjali, Mohammad Reza,Emami, Saeed,Khoobi, Mehdi,Foroumadi, Alireza
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p. 600 - 614
(2018/06/26)
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- Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation
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A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer's disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC50 values of 0.0068 μM and 0.0089 μM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114 μM for hAChE; 0.101 μM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500 mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold.
- He, Qi,Liu, Jing,Lan, Jin-Shuai,Ding, Jiaoli,Sun, Yongbing,Fang, Yuanying,Jiang, Neng,Yang, Zunhua,Sun, Liyuan,Jin, Yi,Xie, Sai-Sai
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supporting information
p. 512 - 528
(2018/09/29)
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- Nitric oxide donor type coumarin derivatives, preparation methods therefor and medicinal use of nitric oxide donor type coumarin derivatives
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The invention relates to the fields of pharmacochemistry and pharmacotherapeutics and particularly relates to nitric oxide donor type coumarin derivatives, preparation methods therefor and an application of the nitric oxide donor type coumarin derivatives. The compounds play a role in resisting tumors and can be applied to the preparation of antitumor drugs.
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- The novel compound having a coumarin and peptides, their nanoparticles and carrier for drug delivery thereof comprising the same
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The present invention relates to a novel compound comprising a structure (Peptide-coumarin-triphenylphosphonium structure) in which one end of a coumarin group is connected to a hydrophobic peptide group and the other end is connected to a hydrophilic tri
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Paragraph 0058-0060
(2017/07/14)
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- Coumarin derivative and preparation method thereof
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The invention relates to a coumarin derivative and a preparation method thereof. Specifically, the invention discloses novel 7-hydroxycoumarin-3-formyl-beta-alanyl aminoacyl-2-aminomethyl pyridine with anti-inflammatory activities, which is shown in a gen
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Paragraph 0039; 0040
(2017/05/19)
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- Fluorogenic probes to monitor cytosolic phospholipase A2 activity
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Arachidonic acid derivatives equipped with either one or two fluorescent groups attached to the tip of the alkyl chains were synthesized and shown to function as inhibitor and substrate probes of cPLA2. The inhibitor probe was demonstrated to p
- Ng, Cheng Yang,Kwok, Timothy Xiong Wei,Tan, Francis Chee Kuan,Low, Chian-Ming,Lam, Yulin
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supporting information
p. 1813 - 1816
(2017/02/10)
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- PhI(OAc)2 mediated an efficient Knoevenagel reaction and their synthetic application for coumarin derivatives
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A phenyliododiacetate (PhI(OAc)2) mediated an efficient and novel protocol for the Knoevenagel reaction has been successfully accomplished. A base free, simple and straightforward method afforded wide substrate scope and good functional group tolerance, having high yields (80–92%) under environmentally benign and mild reaction conditions.
- Khan, Danish,Mukhtar, Sayeed,Alsharif, Meshari A.,Alahmdi, Mohammed Issa,Ahmed, Naseem
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supporting information
p. 3183 - 3187
(2017/07/18)
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- O-prenylated 3-carboxycoumarins as a novel class of 15-LOX-1 inhibitors
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Allyloxy, Isopentenyloxy, geranyloxy and farnesyloxy derivatives of 3-carboxycoumarin, at position 5, 6, 7, and 8, were synthesized and their inhibitory potency against human 15- lipoxygenase-1 (human 15-LOX-1) were determined. Among the synthetic coumarins, Oallyl and O-isopentenyl derivatives demonstrated no considerable lipoxygenase inhibition while O-geranyl and O-farnesyl derivatives demonstrated potent inhibitory activity. 5-farnesyloxy- 3-carboxycoumarin demonstrated the most potent inhibitory activity by IC50 = 0.74 μM while 6-farnesyloxy-3-carboxycoumarin was the weakest inhibitor among farnesyl analogs (IC50 = 10.4 μM). Bonding affinity of the designed molecular structures toward 15- LOX-1 3D structure complexed with RS75091, as potent 15-LOX-1 inhibitor, was studied by utilizing docking analysis. There was a direct relationship between lipoxygenase inhibitory potency and prenyl length chain. The ability of the prenyl portion to fill the lipophilic pocket which is formed by Ile663, Ala404, Arg403, Ile400, Ile173 and Phe167 side chains can explain the observed relationship. Similarity rate between the docked models and complexed form of RS75091, from point of view of configuration and conformation, could explain inhibitory potency variation between each prenyloxy substitution of 3-carboxycoumarins.
- Jabbari, Atena,Mousavian, Mina,Seyedi, Seyed Mohamad,Bakavoli, Mehdi,Sadeghian, Hamid
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- Design, synthesis and biological evaluation of novel coumarin-based benzamides as potent histone deacetylase inhibitors and anticancer agents
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Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also viable targets for cancer therapeutics. A novel series of coumarin-based benzamides was designed and synthesized as HDAC inhibitors. The cytotoxic activity of the synthesized compounds (8a-u) was evaluated against six human cancer cell lines including HCT116, A2780, MCF7, PC3, HL60 and A549 and a single normal cell line (Huvec). We evaluated their inhibitory activities against pan HDAC and HDAC1 isoform. Four compounds (8f, 8q, 8r and 8u) showed significant cytotoxicity with IC50 in the range of 0.53–57.59?μM on cancer cells and potent pan-HDAC inhibitory activity (consists of HDAC isoenzymes) (IC50?=?0.80–14.81?μM) and HDAC1 inhibitory activity (IC50?=?0.47–0.87?μM and also, had no effect on Huvec (human normal cell line) viability (IC50?>?100?μM). Among them, 8u displayed a higher potency for HDAC1 inhibition with IC50 value of 0.47?±?0.02?μM near equal to the reference drug Entinostat (IC50?=?0.41?±?0.06?μM). Molecular docking studies and Molecular dynamics simulation of compound 8a displayed possible mode of interaction between this compound and HDAC1enzyme.
- Abdizadeh, Tooba,Kalani, Mohammad Reza,Abnous, Khalil,Tayarani-Najaran, Zahra,Khashyarmanesh, Bibi Zahra,Abdizadeh, Rahman,Ghodsi, Razieh,Hadizadeh, Farzin
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- β-Alanyl aminopeptidase-activated fluorogenic probes for the rapid identification of Pseudomonas aeruginosa in clinical samples
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The fluorogenic self-immolative substrates 8 are specifically hydrolyzed by β-alanyl aminopeptidase, resulting in a 1,6-elimination and the release of the highly fluorescent hydroxycoumarins 6. 7-{4-(β-Alanylamino)}benzyloxy-3-ethoxycarbonylcoumarin trifluoroacetate 8b has advantages over another fluorogenic substrate, 7-N-β-alanylamino-4-methylcoumarin 9, as it is retained by bacterial colonies in solid agar applications, and results in similar times to detection, stronger fluorescence intensities, and no decrease in signal over time in liquid media. Although 7-{4-(β-alanylamino)}benzyloxy-4-methylcoumarin trifluoroacetate 8a produces a weaker signal than substrate 8b, its use allowed better discrimination between the BAP producers P. aeruginosa (positive) and S. marcescens (negative).
- Váradi, Linda,Hibbs, David E.,Orenga, Sylvain,Babolat, Michèle,Perry, John D.,Groundwater, Paul W.
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p. 58884 - 58889
(2016/07/06)
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- Design, synthesis and cytotoxicity of novel dihydroartemisinin-coumarin hybrids via click chemistry
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In order to develop novel chemotherapeutic agents with potent anticancer activities, we designed four series of novel compounds employing hybridization strategy. Twenty novel dihydroartemisinin-coumarin hybrids, 10a-e, 11a-e, 12a-e, 13a-e, were synthesized via click chemistry in this study and their structures were characterized by HRMS and NMR. The cytotoxic activities were measured by MTT assay against three cancer cell lines (HCT-116, MDA-MB-231, and HT-29) under normoxic or anoxic conditions, respectively. The target compounds exhibited moderate activity with IC50 values in the 0.05-125.40 μM range, and these compounds exhibited better activity against HT-29 cell line under anoxic condition. The cytotoxic activities of most compounds under anoxic condition displayed one- to 10-fold greater activity than under normoxic condition. Compounds 10a - e showed better selectivity against the HT-29 cell line than the other two cell lines. These results indicated that our design of CA IX inhibitors does correspond with its action mode to some degree and deserves further investigation.
- Tian, Ye,Liang, Zhen,Xu, Hang,Mou, Yanhua,Guo, Chun
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- 1,2,3-Triazole incorporated coumarin derivatives as potential antifungal and antioxidant agents
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A series of novel ethyl-7-((1-(benzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-oxo-2H-chromene-3-carboxylates 8a-h as potential antifungal agents were synthesized via click chemistry. The antifungal activity was evaluated against five human pathogenic fungal strains, such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. Compound 8c, 8d, 8e and 8h were found to be equipotent against C. albicans when compared with miconazole and compound 8f was found to be two-fold more active compared with miconazole and equipotent to fluconazole against C. albicans. The coumarin-based triazole derivatives were also evaluated for antioxidant activity and compound 8a was found to be potent antioxidant when compared with standard drug. Furthermore, molecular docking study of the newly synthesized compounds was performed and results showed good binding mode in the active site of fungal C. albicans enzyme P450 cytochrome lanosterol 14α-demethylase. Moreover, the synthesized compounds were also analyzed for ADME properties and showed potential to build up as good oral drug candidates.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.
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p. 295 - 301
(2018/03/22)
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- Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety
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A number of N-(2-(1H-indol-3-yl)ethyl)-2-oxo-2H-chromene-3-carboxamides were synthesized and tested against AChE and BuChE. The in?vitro assessment of the synthesized compounds 4a-o revealed that most of them had significant activity toward AChE. The SAR study demonstrated that the introduction of benzyloxy moiety on the 7-position of coumarin scaffold can improve the anti-AChE activity. The best result was obtained with 7-(4-fluorobenzyl)oxy moiety in the case of compound 4o, displaying IC50value of 0.16?μM. Based on the docking study of AChE, the prototype compound 4o was laid across the active site and occupied both peripheral anionic site (PAS) and catalytic anionic site (CAS).
- Ghanei-Nasab, Samaneh,Khoobi, Mehdi,Hadizadeh, Farzin,Marjani, Azam,Moradi, Alireza,Nadri, Hamid,Emami, Saeed,Foroumadi, Alireza,Shafiee, Abbas
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- Selective selenol fluorescent probes: Design, synthesis, structural determinants, and biological applications
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Selenium (Se) is an essential micronutrient element, and the biological significance of Se is predominantly dependent on its incorporation as selenocysteine (Sec), the genetically encoded 21st amino acid in protein synthesis, into the active site of selenoproteins, which have broad functions, ranging from redox regulation and anti-inflammation to the production of active thyroid hormones. Compared to its counterpart Cys, there are only limited probes for selective recognition of Sec, and such selectivity is strictly restricted at low pH conditions. We reported herein the design, synthesis, and biological evaluations of a series of potential Sec probes based on the mechanism of nucleophilic aromatic substitution. After the initial screening, the structural determinants for selective recognition of Sec were recapitulated. The follow-up studies identified that probe 19 (Sel-green) responds to Sec and other selenols with more than 100-fold increase of emission in neutral aqueous solution (pH 7.4), while there is no significant interference from the biological thiols, amines, or alcohols. Sel-green was successfully applied to quantify the Sec content in the selenoenzyme thioredoxin reductase and image endogenous Sec in live HepG2 cells. With the aid of Sel-green, we further demonstrated that the cytotoxicity of different selenocompounds is correlated to their ability metabolizing to selenols in cells. To the best of our knowledge, Sel-green is the first selenol probe that works under physiological conditions. The elucidation of the structure-activity relationship for selective recognition of selenols paves the way for further design of novel probes to better understand the pivotal role of Sec as well as selenoproteins in vivo.
- Zhang, Baoxin,Ge, Chunpo,Yao, Juan,Liu, Yaping,Xie, Huichen,Fang, Jianguo
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p. 757 - 769
(2015/01/30)
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- Bioorthogonal Enzymatic Activation of Caged Compounds
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Engineered cytochrome P450 monooxygenase variants are reported as highly active and selective catalysts for the bioorthogonal uncaging of propargylic and benzylic ether protected substrates, including uncaging in living E. coli. observed selectivity is supported by induced-fit docking and molecular dynamics simulations. This proof-of-principle study points towards the utility of bioorthogonal enzyme/protecting group pairs for applications in the life sciences.
- Ritter, Cornelia,Nett, Nathalie,Acevedo-Rocha, Carlos G.,Lonsdale, Richard,Kr?ling, Katja,Dempwolff, Felix,Hoebenreich, Sabrina,Graumann, Peter L.,Reetz, Manfred T.,Meggers, Eric
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supporting information
p. 13440 - 13443
(2015/11/09)
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- A Dual-Response Fluorescent Probe Reveals the H2O2-Induced H2S Biogenesis through a Cystathionine β-Synthase Pathway
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The two signaling molecules H2S and H2O2 play key roles in maintaining intracellular redox homeostasis. The biological relationship between H2O2 and H2S remains largely unknown in redox biology. In this study, we rationally designed and synthesized single- and dual-response fluorescent probes for detecting both H2O2 and H2S in living cells. The dual-response probe was shown to be capable of mono- and dual-detection of H2O2 and H2S selectively and sensitively. Detailed bioimaging studies based on the probes revealed that both exogenous and endogenous H2O2 could induce H2S biogenesis in living cells. By using gene-knockdown techniques with bioimaging, the H2S biogenesis was found to be majorly cystathionine β-synthase (CBS)-dependent. Our finding shows the first direct evidence on the biological communication between H2O2 (ROS) and H2S (RSS) in vivo. CBS is responsible: A fluorescent probe with two heads for H2O2 and H2S reveals that both exogenous and endogenous H2O2 molecules can induce endogenous H2S biogenesis on a cystathionine β-synthase (CBS) pathway (see scheme).
- Yi, Long,Wei, Lv,Wang, Runyu,Zhang, Changyu,Zhang, Jie,Tan, Tianwei,Xi, Zhen
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supporting information
p. 15167 - 15172
(2015/11/02)
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