- A Cyanine Photooxidation/β-Elimination Sequence Enables Near-infrared Uncaging of Aryl Amine Payloads
-
Uncaging strategies that use near-infrared wavelengths can enable the highly targeted delivery of biomolecules in complex settings. Many methods, including an approach we developed using cyanine photooxidation, are limited to phenol-containing payloads. Given the critical role of amines in diverse biological processes, we sought to use cyanine photooxidation to initiate the release of aryl amines. Heptamethine cyanines substituted with an aryl amine at the C4′ position undergo only inefficient release, likely due electronic factors. We then pursued the hypothesis that the carbonyl products derived from cyanine photooxidation could undergo efficient β-elimination. After examining both symmetrical and unsymmetrical scaffolds, we identify a merocyanine substituted with indolenine and coumarin heterocycles that undergoes efficient photooxidation and aniline uncaging. In total, these studies provide a new scheme—cyanine photooxidation followed by β-elimination—through which to design photocages with efficient uncaging properties.
- Yamamoto, Tsuyoshi,Caldwell, Donald R.,Gandioso, Albert,Schnermann, Martin J.
-
-
Read Online
- Illuminating the Function of the Hydroxyl Radical in the Brains of Mice with Depression Phenotypes by Two-Photon Fluorescence Imaging
-
Depression is intimately linked with oxidative stress. As one of the most reactive and oxidative reactive oxygen species that is overproduced during oxidative stress, the hydroxyl radical (.OH) can cause macromolecular damage and subsequent neurological diseases. However, due to the high reactivity and low concentration of .OH, precise exploration of .OH in brains remains a challenge. The two-photon fluorescence probe MD-B was developed for in situ .OH imaging in living systems. This probe achieves exceptional selectivity towards .OH through the one-electron oxidation of 3-methyl-pyrazolone as a new specific recognition site. MD-B can be used to map .OH in mouse brain, thereby revealing that increased .OH is positively correlated with the severity of depression phenotypes. Furthermore, .OH has been shown to inactivate deacetylase SIRT1, thereby leading to the occurrence and development of depression phenotypes. This work provides a new strategy for the future treatment of depression.
- Wang, Xin,Li, Ping,Ding, Qi,Wu, Chuanchen,Zhang, Wen,Tang, Bo
-
-
Read Online
- Multi-Fluorinated Azido Coumarins for Rapid and Selective Detection of Biological H2S in Living Cells
-
Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule with multiple biological functions. In order to visualize the endogenous in situ production of H2S in living cells in real time, here we developed multi-fluorinated azido coumarins as fluorescent probes for the rapid and selective detection of biological H2S. Kinetic studies indicated that an increase in fluorine substitution leads to an increased rate of H2S-mediated reduction reaction, which is also supported by our theoretical calculations. To our delight, tetra-fluorinated coumarin 1 could react with H2S fast (t1/2≈1 min) and selectively, which could be further used for continuous enzymatic assays and for visualization of intracellular H2S. Bioimaging results obtained with 1 revealed that d-Cys could induce a higher level of endogenous H2S production than l-Cys in a time-dependent manner in living cell.
- Zhu, Zhentao,Li, Yanyan,Wei, Chao,Wen, Xin,Xi, Zhen,Yi, Long
-
-
Read Online
- Benzopyrone or quinolinone compound and application thereof
-
The invention discloses a benzopyrone or quinolinone compound and application thereof in preparation of a medicine for treating prostatic cancer, and belongs to the field of medicines. The benzopyroneand quinolinone compound with the structural formula as shown in the formula (I) has obvious antagonistic activity on androgen receptors and also has inhibitory activity on prostate cancer cells which do not express the androgen receptors. Therefore, the compound can be used as an androgen receptor antagonist to be applied to treatment of diseases related to androgen receptors or treatment of various metastatic prostate cancers, and a new choice is provided for development of drugs for treating prostate cancers.
- -
-
Paragraph 0163-0165
(2020/08/25)
-
- Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents
-
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
-
p. 434 - 449
(2018/04/14)
-
- IS100- A Highly Effective Enzyme Principle For Use In Dermal Therapeutics, And For Health And Beauty
-
A aqueous preparation called IS 100 consisting of at least a hundred of proteins prepared from wheat germ lysate is provided. The preparation shows protease activity and is considerably stable. None of the constituent proteins in IS 100 can permeate synthetic or biological membranes and therefore IS 100 has a variety of in vitro or external applications that require cleaving and cleansing of unwanted or dead tissues on dermal surface.
- -
-
Page/Page column 4
(2016/05/02)
-
- Disassembly kinetics of quinone-methide-based self-immolative spacers that contain aromatic nitrogen heterocycles
-
We prepared several pyridine- and pyrimidine-based self-immolative spacer groups to evaluate the significance of the resonance energy of the spacer aromatic ring on the kinetics of 1,4- and 1,6-elimination reactions, which govern spacer disassembly. Subsequently, we relied on a photoactivation procedure to accurately analyze the disassembly kinetics. Beyond providing new results that are relevant for deriving quantitative structure-property relationships, herein, we demonstrate that pH value can be used as an efficient parameter to finely control the disassembly time of a self-immolative spacer after an initial activation. Burn rubber: Kinetic analysis of the pH-dependent disassembly of self-immolative spacers that contain aromatic nitrogen heterocycles was performed. Electron-poor pyrimidine cores exhibited the longest disassembly times. This study confirms the trend that electron-rich aryl cores accelerate self-immolation.
- Alouane, Ahmed,Labruere, Raphael,Silvestre, Katherine J.,Le Saux, Thomas,Schmidt, Frederic,Jullien, Ludovic
-
p. 1334 - 1340
(2014/05/06)
-
- Magnesium bis(trifluoromethane)sulfonimide: An efficient catalyst for the synthesis of coumarins under solvent-free conditions
-
Magnesium bis(trifluoromethane)sulfonimide [Mg(NTf2) 2] is an efficient catalyst for the synthesis of coumarins via the Pechmann condensation reaction of phenols and β-ketoesters under solvent-free conditions.
- Wang, Hongshe
-
p. 411 - 414
(2013/05/21)
-
- Uncovering the true mechanism of optical detection of HSO4 - in water by Schiff-base receptors - Hydrolysis vs. hydrogen bonding
-
The mechanism of optical detection of HSO4- in aqueous medium by Schiff-base receptors has previously been proposed to depend on selective hydrogen-bond interactions. Here, we clearly demonstrate for the first time that the acidic na
- Kumar, Virendra,Kumar, Ajit,Diwan, Uzra,Upadhyay
-
p. 9540 - 9542
(2012/11/06)
-
- Development of a new enzyme-responsive self-immolative spacer conjugate applicable to the controlled drug release
-
A new self-immolative spacer conjugate based on a chemical adaptor unit aiming at controlled releasing drugs was designed and synthesized. It releases a fluorophore which was used as a model drug via a spontaneous cyclization mechanism after cleavage of an enzyme substrate. This system was proved to be stable under physiological conditions and only decomposed triggered by enzyme. It provides a generic linkage allowing connection of a variety of drugs and targeted devices to the chemical adaptor.
- Jin, Hui-Juan,Lu, Jing,Wu, Xue
-
experimental part
p. 3465 - 3469
(2012/08/08)
-
- Substrate specificity of acetoxy derivatives of coumarins and quinolones towards Calreticulin mediated transacetylation: Investigations on antiplatelet function
-
Calreticulin transacetylase (CRTAase) is known to catalyze the transfer of acetyl group from polyphenolic acetates (PA) to certain receptor proteins (RP), thus modulating their activity. Herein, we studied for the first time the substrate specificity of CRTAase towards N-acetylamino derivatives of coumarins and quinolones. This study is endowed with antiplatelet action by virtue of causing CRTAase catalyzed activation of platelet Nitric Oxide Synthase (NOS) by way of acetylation leading to the inhibition of ADP/Arachidonic acid (AA)-dependent platelet aggregation. Among all the N-acetylamino/acetoxy coumarins and quinolones screened, 7-N-acetylamino-4-methylcoumarin (7-AAMC, 17) was found to be the superior substrate to platelet CRTAase and emerged as the most promising antiplatelet agent both in vitro and in vivo. Further it caused the inhibition of cyclooxygenase-1 (Cox-1) resulting in the down regulation of thromboxane A2 (TxA2), modulation of tissue factor and the inhibition of platelet aggregation. It was also found effective in the inhibition of LPS induced pro-thrombotic conditions.
- Kathuria, Abha,Priya, Nivedita,Chand, Karam,Singh, Prabhjot,Gupta, Anjali,Jalal, Sarah,Gupta, Shilpi,Raj, Hanumantharao G.,Sharma, Sunil K.
-
p. 1624 - 1638
(2012/05/04)
-
- Synthesis, enzymatic evaluation, and docking studies of fluorogenic caspase 8 tetrapeptide substrates
-
The synthesis, enzymatic evaluation, and molecular modeling studies of new fluorogenic tetrapeptide-based substrates selective for caspase 8, having the general structure Ac-IETD-AXX, are described. Various fluorescent reporter groups (AXX), i.e., 3- and 4-substituted coumarins and quinolin-2(1H)-ones were synthesized by von Pechmann condensation. They were subsequently coupled with the caspase-8-selective tetrapeptide Ac-IETD-OH under newly developed synthetic conditions to give the desired substrates in good yields and in high enantiomeric purity. Based on KM and Vmax values, the new compounds proved to be excellent substrates for recombinant human caspase 8. In contrast, the KM values for the same compounds as substrates for human caspase 3 were approximately 10-20-fold higher. Molecular modeling studies based on the X-ray crystal structures of both human caspases 3 and 8 revealed that there is sufficient room within both active sites to accommodate substrates with moderately bulky substituents in the 3- and 4-positions of the fluorogenic coumarins and quinolin-2(1H)-ones. Automated docking of the substrates into the active sites of both human caspases 3 and 8 with the program Auto-Dock 3 gave structures similar to the published crystallographic structures for the same tetrapeptide bound to caspase 8 in the form of an irreversible inhibitor. The calculated binding energies for the new substrates to either caspase 3 or 8 showed little difference between the substrates, consistent with the K M data. In addition, the calculated binding energies (ΔG) to caspase 8 were considerably more negative than those to caspase 3, also consistent with the KM data. A possible molecular interaction that might explain the selectivity of the IETD tetrapeptide motif for caspase 8 over caspase 3 is discussed.
- Reszka, Przemyslaw,Schulz, Riad,Methling, Karen,Lalk, Michael,Bednarski, Patrick J.
-
experimental part
p. 103 - 117
(2010/11/02)
-
- Ground and excited states calculations of 7-phenylamino-substituted coumarins
-
A theoretical calculation of the ground and first excited states of two 7-phenylamino-substituted coumarin compounds are performed. In order to study the effect of phenyl substituted in amino group and fluorine atoms substituted in methyl group, 7-amino-4-methyl coumarin (C120) and 7-amino-4-(trifluoromethyl) coumarin (C151) were also studied. The geometries of the ground state and the first ground state were optimized using density function theory and configuration interaction singles levels of theory. Molecular orbitals (MO) of the ground and first excited states of the four coumarin compounds were obtained to explain the change of the structures. ZINDO and TD-DFT methods with different basis sets were applied to predict the UV absorption spectra. The solvent effect had also been taken into account using self-consistent isodensity polarized continuum model. The predicted spectra are in agreement with the experimental data. Crown Copyright
- Xu, Bo,Yang, Jing,Jiang, Xuesong,Wang, Yuanlong,Sun, Huai,Yin, Jie
-
experimental part
p. 15 - 20
(2009/03/12)
-
- Activatable probes and methods for in vivo gene detection
-
Probes for detecting a target polynucleotide are provided. One aspect provides a molecular beacon probe set wherein the donor molecular beacon comprises a quantum dot and an acceptor molecular beacon comprises at least one reporter. The probes optionally comprise a protein transduction domain, targeting signal, or a combination thereof. Methods for detecting target polynucleotides using the disclosed probes are also provided.
- -
-
-
- Application of 2D-fluorescence spectroscopy for on-line monitoring of pseudoenantiomeric transformations in supercritical carbon dioxide systems
-
2D-Fluorescence spectroscopy has been shown to be effective for the on-line monitoring of spectroscopic detectable substrates L-phenylalanine-7-amido-4- methylcoumarine (L-PheAMC) and D-phenylalanine-7-amido-4- trifluoromethylcoumarine (D-PheAFC) in supercritical carbon dioxide. Earlier investigations with the coumarine substrates in watery and organic phases showed their potential for on-line enantiomeric evaluations of enzymatic reactions in different reaction media. The solubility of the different substrates and their fluorescence maximums were investigated in SCCO2. The sole hydrolyzations of L-PheAMC and D-PheAFC with α-chymotrypsin and the esterase from porcine liver were tracked on-line in the supercritical medium; however, different solubility characteristics of the methyl- and trifluoromethyl-substituted coumarins influence the simultaneous detection of the L- and D-substrate within the applied high-pressure reactor system.
- Knuettel, Torsten,Meyer, Hartmut,Scheper, Thomas
-
p. 6184 - 6189
(2008/02/03)
-
- Dual resonance energy transfer nucleic acid probes
-
Dual nucleic acid probes with resonance energy transfer moieties are provided. In particular, fluorescent or luminescent resonance energy transfer moieties are provided on hairpin stem-loop molecular beacon probes that hybridize sufficiently near each other on a subject nucleic acid, e.g. mRNA, to generate an observable interaction. The invention also provides lanthanide chelate luminescent resonance energy transfer moieties on linear and stem-loop probes that hybridize sufficiently near each other on a subject nucleic acid to generate an observable interaction. The invention thereby provides detectable signals for rapid, specific and sensitive hybridization determination in vivo. The probes are used in methods of detection of nucleic acid target hybridization for the identification and quantification of tissue and cell-specific gene expression levels, including response to external stimuli, such as drug candidates, and genetic variations associated with disease, such as cancer.
- -
-
-
- The indium(III) chloride-catalyzed von Pechmann reaction: A simple and effective procedure for the synthesis of 4-substituted coumarins
-
Indium(III) chloride is used as an efficient catalyst in the von Pechmann condensation of phenols with β-ketoesters leading to the formation of coumarin derivatives in excellent yields with good purity.
- Subhas Bose,Rudradas,Hari Babu, Mereyala
-
p. 9195 - 9197
(2007/10/03)
-
- The contribution of secondary proton bridges to the catalytic power of the serine proteases
-
The curvature of proton-inventory functions (rate constants in mixtures of protium and deuterium oxides) for hydrolysis of substrates of varying structure by trypsins from four different sources has been used as a signal of transition-state stabilization by a short, strong hydrogen bonds ("low-barrier hydrogen bonds") at the histidine-aspartate site of the catalytic triad. Previous estimates suggested contributions as large as 85 kJ mol-1 but the current findings are consistent with contributions of no more than a few kJ mol-1. WILEY-VCH Verlag GmbH, 1998.
- Bibbs, Jeffrey A.,Garoutte, Michael P.,Wang, Bing,Tittel, Paul D.,Barbara Schowen,Schowen, Richard L.
-
p. 573 - 579
(2007/10/03)
-
- Some 7-Substituted 4-(Trifluoromethyl)coumarins
-
Preparation and spectral properties are given for 13 substituted 4-(trifluoromethyl)coumarins (7-hydroxy, 7,8-dihydroxy, 6-ethyl-7-hydroxy, 6-benzyl-7-hydroxy, 7-methoxy, 7-methyl, 7-amino, 7-(ethylamino), 7-(benzylamino), 7-anilino, 7-, 7-, and 2(1H)-isoindolyl).Three 7-(acylamido)-4-(trifluoromethyl)coumarins (acetyl, benzoyl, and bromoacetyl) were also prepared as well as two new phenol precursors, 3-phenol and 2-(3-hydroxyphenyl)-1H-isoindole.
- Bissell, Eugene R.,Larson, D. Kristin,Croudace, Michael C.
-
p. 348 - 350
(2007/10/02)
-
- Synthesis and Chemistry of 7-Amino-4-(trifluoromethyl)coumarin and Its Amino Acid and Peptide Derivatives
-
The synthesis and purification of 7-amino-4-(trifluoromethyl)coumarin, a novel fluorescent marker for the sensitive detection of proteinases, were investigated.Two byproducts, 7-hydroxy-4-(trifluoromethyl-2-quinolone and 2-ethoxy-7-hydroxy-4-(trifluoromethyl)quinoline, were isolated and identified. 7-Methoxy-4-(trifluoromethyl)-2-quinolone was also prepared.Amino acid and peptide derivatives prepared by solution methods using the stepwise approach included 7-(L-leucinamido)-, 7-(D-alanyl-L-leucyl-L-lysinamido)-, 7-(D-valyl-L-leucyl-L-lysinamido)-, and 7-(Nα-Z-glycylglycyl-L-argininamido)-4-(trifluoromethyl)coumarins
- Bissell, Eugene R.,Mitchell, Alexander R.,Smith, Robert E.
-
p. 2283 - 2287
(2007/10/02)
-
