- Cyclization Reaction-Based Turn-on Probe for Covalent Labeling of Target Proteins
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Fluorescent molecules have contributed to basic biological research but there are currently only a limited number of probes available for the detection of non-enzymatic proteins. Here, we report turn-on fluorescent probes mediated by conjugate addition and cyclization (TCC probes). These probes react with multiple amino acids and exhibit a 36-fold greater emission intensity after reaction. We analyzed the reactions between TCC probes and nuclear receptors by electrospray ionization mass spectrometry, X-ray crystallography, spectrofluorometry, and fluorescence microscopy. In vitro analysis showed that probes consisting of a protein ligand and TCC could label vitamin D receptor and peroxisome proliferator-activated receptor γ. Moreover, we demonstrated that not only a ligand unit but also a peptide unit can label the target protein in a complex mixture. Non-enzymatic proteins are challenging targets for turn-on probes. Here, Kojima et al. report turn-on fluorescent probes mediated by conjugate addition and cyclization (TCC probes). These probes react with nuclear receptors and emit bright fluorescence after the reaction. TCC probes are potent tools for molecular imaging and chemical proteomics.
- Fujita, Yuki,Ikebe, Yuka,Itoh, Toshimasa,Kojima, Hiroyuki,Ohashi, Nami,Takeuchi, Ryosuke,Yamamoto, Keiko
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p. 334 - 349
(2020/03/17)
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- A Copper Halide Promoted Regioselective Halogenation of Coumarins Using N-Halosuccinimide as Halide Source
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A safe, convenient, and regioselective synthesis of 3-halo coumarins using a metal halide (CuX 2 alone or with ZnX 2) promoted halogenation with N -halosuccinimide (NXS) as halide source is reported. The synthesis involved the steady in situ generation of highly reactive positive halogen (X +) by the coordination of copper or zinc with the N -halosuccinimide and subsequent electrophilic aromatic substitution of the electron-deficient coumarins. This procedure works well also for the halogenation of less electron-rich naphthoquinones, flavones, and methoxypsoralen in moderate to quantitative yields. This protocol features simple experimental conditions using readily available inexpensive reagents and provides a convenient approach to the chlorination or bromination of some useful heteroaromatic compounds.
- Su, Jinling,Zhang, Yan,Chen, Mingren,Li, Weiming,Qin, Xuewei,Xie, Yanping,Qin, Lixiao,Huang, Shihua,Zhang, Min
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supporting information
p. 630 - 634
(2019/03/08)
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- Discovery of fluorescent 3-heteroarylcoumarin derivatives as novel inhibitors of anaplastic lymphoma kinase
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Altered expression or hyperactivation of anaplastic lymphoma kinase (ALK), as a consequence of translocations or point mutations, is one of the main oncogenic drivers in non-small cell lung cancer. Using structure-based design and in vitro enzyme assays, we identified 3-heteroarylcoumarin as a new template for the development of novel fluorescent ALK inhibitors. Molecular simulation provided structural insights for the design of 3-heteroarylcoumarin derivatives, which were easily prepared through efficient synthetic approaches including direct C-H cross coupling. Importantly, these coumarin-based ALK inhibitors can be tracked using microscopy techniques: we illustrated the use of the most potent compound in this series, 5a, (ALK/IC50 = 0.51 μM, λemi = 500 nm, φF = 0.29) to monitor its subcellular distribution pattern by confocal fluorescence microscopy.
- Mah, Shinmee,Song, Daesun,Shin, Yongje,Jung, Yongwon,Hong, Sungwoo,Jang, Jaebong,Latif, Muhammad
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p. 186 - 194
(2019/01/11)
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- Dual functional small molecule fluorescent probes for image-guided estrogen receptor-specific targeting coupled potent antiproliferative potency for breast cancer therapy
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A strategy by integrating biological imaging into early stages of the drug discovery process can improve our understanding of drug activity during preclinical and clinical study. In this article, we designed and synthesized coumarin-based nonsteroidal type fluorescence ligands for drug-target binding imaging. Among these synthesized compounds, 3e, 3f and 3h showed potent ER binding affinity and 3e (IC50?=?0.012?μM) exhibited excellent ERα antagonistic activity, its antiproliferative potency in breast cancer MCF-7 cells is equipotent to the approved drug tamoxifen. The fluorescence of compounds 3e and 3f depended on the solvent properties and showed significant changes when mixed with ERα or ERβ in vitro. Furthermore, target molecule 3e could cross the cell membrane, localize and image drug-target interaction in real time without cell washing. Thus, the coumarin-based platform represents a promising new ER-targeted delivery vehicle with potential imaging and therapeutic properties.
- Yang, Lu,Hu, Zhiye,Luo, Junjie,Tang, Chu,Zhang, Silong,Ning, Wentao,Dong, Chune,Huang, Jian,Liu, Xianjun,Zhou, Hai-Bing
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p. 3531 - 3539
(2017/05/29)
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- Novel coumarin compound and application thereof
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The invention relates to the technical field of novel materials and organic chemicals, in particular to a novel compound, a process technology for chemically preparing the novel compound, application of the novel compound and a radiation curing formula pr
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Paragraph 0045; 0047
(2017/08/29)
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- A new highly selective and sensitive fluorescent probe for Zn2+ and its application in cell-imaging
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A new fluorescent probe, 3-((4-([2,2′:6′,2″-terpyridin]- 4′-yl)phenyl)ethynyl)-7-methoxy-2H-chromen-2-one (ZC-F7) composed of coumarin as the fluorophore and terpyridine as the receptor is designed and synthesized. Based on the intramolecular charge transfer (ICT) effect, the probe exhibits significant variation on emission wavelengths with shifts more than 100 nm after combined with Zn2+, in accordance with the conversion of emission colors from blue to green. Good selectivity and sensitivity of this probe towards Zn2+ can be found even on the ppb level in aqueous solution. The Job's plot test suggests a 1:1 stoichiometry between ZC-F7 and Zn2+. The application of the fluorescence probe in bio-imaging is also demonstrated, proving its potential usage in fields such as environment protection, water treatment and safety inspection.
- Hu, Quan,Tan, Yiqun,Liu, Min,Yu, Jiancan,Cui, Yuanjing,Yang, Yu
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- An efficient regioselective bromination protocol of activated coumarins using 2,4,4,6-tetrabromo-2,5-cyclohexadienone
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2,4,4,6-Tetrabromo-2,5-cyclohexadienone mediated bromination of a wide assortment of activated coumarins in acetonitrile has been accomplished with high regioselectivity and good to excellent yields. The selectivity and efficiency of bromination were found to be markedly dependent on electronic factors, particularly degree of electron withdrawal from electron-releasing 7-oxygenated substituents to the C-3 position of the α-pyrone moiety by vinylogous resonance and the presence of nucleophilic additives such as water and tetra-n-butylammonium bromide in the reaction medium. The sole by-product of the reaction was converted back to the reagent by oxidation with KBr-KBrO 3, which was recycled three times without significant loss of efficiency.
- Ganguly, Nemai C.,Nayek, Subhasis,Chandra, Sumanta
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supporting information
p. 1155 - 1159
(2013/11/06)
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- Dioxane dibromide mediated bromination of substituted coumarins under solvent-free conditions
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An efficient solvent-free protocol for regioselective bromination of substituted coumarins has been developed by using dioxane dibromide as the solid brominating agent. The efficacy of the solvent-free protocol has been established. The effects of the electronic nature and location of the substituents on the outcome of the reaction have been rationalized with a proposed mechanism.
- Chaudhuri, Subrata Kumar,Roy, Sanchita,Bhar, Sanjay
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supporting information; experimental part
p. 323 - 329
(2012/05/04)
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- 3-arylcoumarin derivatives manifest anti-proliferative activity through Hsp90 inhibition
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The potential therapeutic benefits associated with Hsp90 modulation for the treatment of cancer and neurodegenerative diseases highlight the importance of identifying novel Hsp90 scaffolds. KU-398, a novobiocin analogue, and silybin were recently identified as new Hsp90 inhibitors. Consequently, a library of 3-arylcoumarin derivatives that incorporated the structural features of KU-398 and silybin was designed, synthesized, and evaluated against two breast cancer cell lines. Western blot analysis confirmed that the resulting 3-arylcoumarin hybrids target the Hsp90 protein folding machinery.
- Zhao, Huiping,Yan, Bin,Peterson, Laura B.,Blagg, Brian S. J.
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p. 327 - 331
(2012/05/20)
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- Expedited synthesis of benzofuran-2-carboxylic acids via microwave-assisted Perkin rearrangement reaction
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3-Halocoumarins are readily converted into benzofuran-2-carboxylic acids via a Perkin (coumarin-benzofuran ring contraction) rearrangement reaction. This rearrangement entails initial base catalyzed ring fission. The resulting phenoxide anion then attacks a vinyl halide to produce the final benzofuran moiety. We explored this reaction under microwave reaction conditions and were able to significantly reduce reaction times as well as obtain very high yields of a series of benzofuran-2-carboxylic acid derivatives.
- Marriott, Karla-Sue C.,Bartee, Rena,Morrison, Andrew Z.,Stewart, Leonard,Wesby, Julian
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experimental part
p. 3319 - 3321
(2012/08/07)
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- A simple synthesis of functionalized 3-bromocoumarins by a one-pot three-component reaction
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Functionalized 3-bromocoumarins 2 have been, prepared, by a simple one-pot bromination/Wittig/cyclization tandem process from methyl (triphenylphosphoranylidene)acetate, Nbromosuccinimide and a series of 2-hydroxybenzaldehydes. Owing to the commercial availability of salicylaldehyde derivatives, this approach offers such a diverse range of compounds that it fulfills the recent demand for the generation of large combinatorial chemical libraries based on the coumarin scaffold
- Audisio, Davide,Messaoudi, Samir,Brion, Jean-Daniel,Alami, Mouad
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experimental part
p. 1046 - 1051
(2010/04/25)
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- Chemistry of Natural Products, Part 155; A Simple Synthesis of 4-(Herniarine-3-yl)-2-methyl-3-buten-2-ol
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A simple synthesis of 4-(herniarine-3-yl)-2-methyl-3-buten-2-ol from umbelliferone in relatively high yield is described. Key words: Umbelliferone, 3-Bromo-herniarine, Heck Reaction, 4-(Herniarine-3-yl)-2-methyl-3-buten-2-ol
- Reisch, Johannes,Zappel, Johannes
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p. 1801 - 1802
(2007/10/02)
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