cas 26093-31-2, Coumarin 120 | Articles data

Articles about 26093-31-2Total 138 be found

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HgII-selective fluorescent indicator: One-step synthesis
Fluorescent indicator 2 was synthesized by a single-step reaction. The indicator underwent an HgII-selective reaction (hydrolysis/ decarboxylation sequence) in the presence of HgII, which was verified by using LC-MS and NMR techniques.
Kim, Seul-Bi,Cho, Dong-Gyu
p. 2495 - 2498
(2012)
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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
(2005)
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Coumarin-coupled receptor as a membrane-permeable, Cu2+- selective fluorescent chemosensor for imaging copper(II) in HEPG-2 cell
A novel fluorescent chemosensor 1 for imaging labile Cu2+ in living biological samples was designed and synthesized; it exhibits very strong fluorescence responses to Cu2+, and its LSM images strongly support the existence of Cu2+ in HEGP-2 cell. Copyright
Wang, Mao-Xiang,Huang, Sheng-Hai,Meng, Xiang-Ming,Zhu, Man-Zhou,Guo, Qing-Xiang
p. 462 - 465
(2008)
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Synthesis of Novel and Thermally Stable Water Insoluble Coumarin-based Azo Dyes via a Mild and Green Procedure
A series of novel azo coumarin dyes were synthesized by the diazotization of 7-amino coumarins in the presence of catalytic amounts of tungstate sulfuric acid (TSA) followed by coupling with phenol derivatives. Tungstate sulfuric acid catalyzes this reaction at room temperature and short reaction time with high yields. A series of novel azo coumarin dyes were synthesized by the diazotization of 7-amino coumarins in the presence of catalytic amounts of tungstate sulfuric acid (TSA) followed by coupling with phenol derivatives. Tungstate sulfuric acid catalyzes this reaction at room temperature and short reaction time with high yields.
Kiani, Mahtab,Karami, Bahador
p. 756 - 760
(2015)
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Organic azide inhibitors of cysteine proteases
Cysteine proteases are crucial regulatory enzymes in human physiology and disease. Inhibitors are usually designed with reactive electrophiles to covalently bond to the catalytic cysteinyl sulfur, and consequently they also indiscriminately interact with biological thiolates and other nucleophiles, leading to toxic side effects in vivo. Here we describe an alternative to using reactive electrophiles, demonstrating the use of a much less reactive azidomethylene substituent (-CH2-N3) that confers potent inhibition of cysteine proteases. This new approach resulted in potent, reversible, competitive inhibitors of caspase-1 (IC50 10 nM), with significant advantages over aldehydes such as high stability in vitro to thiols (10 mM dithiothreitol (pH 7.2), 20 mM glutathione (pH 7.2, 9, 11)) and aqueous media, as well as some highly desirable druglike features. It was also demonstrated that azides can be incorporated into inhibitors of other caspases (e.g. 3, 8) and cathepsins (e.g. K, S, B), indicating the versatility of this valuable new approach to cysteine protease inhibition. Copyright
Le, Giang Thanh,Abbenante, Giovanni,Madala, Praveen K.,Hoang, Huy N.,Fairlie, David P.
p. 12396 - 12397
(2006)
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Natural biflavones as?novel inhibitors of?cathepsin B and?K
Cathepsin B and K, two important members in lysosomal proteases, involve in many serious human diseases, such as tumor and osteoporosis. In order to find their novel inhibitors, we performed the inhibition assays of cathepsin B and cathepsin K in vitro, randomly screened compounds from plants, and found six biflavones, named AMF1-5 and HIF, can potently inhibit cathepsin B and cathepsin K, especially AMF4 and HIF with IC50 of 0.62 and 0.58?μM against cathepsin B. They are novel inhibitors for cathepsin B and K. Inhibition and flexible docking studies indicated that these biflavones are reversible inhibitors of cathepsin B, and their binding patterns and interaction modes with cathepsin B made them more specific to cathepsin B endopeptidase.
Zeng,Pan,Tan,Xiong,Zhang
p. 1247 - 1252
(2006)
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A fluorescent assay suitable for inhibitor screening and vanin tissue quantification
Vanin-1 is a pantetheinase that catalyzes the hydrolysis of pantetheine to produce pantothenic acid (vitamin B5) and cysteamine. Reported here is a highly sensitive fluorescent assay using a novel fluorescently labeled pantothenate derivative. The assay has been used for characterization of a soluble version of human vanin-1 recombinant protein, identification and characterization of hits from high-throughput screening (HTS), and quantification of vanin pantothenase activity in cell lines and tissues. Under optimized assay conditions, we quantified vanin pantothenase activity in tissue lysate and found low activity in lung and liver but high activity in kidney. We demonstrated that the purified recombinant vanin-1 consisting of the extracellular portion without the glycosylphosphatidylinositol (GPI) linker was highly active with an apparent Km of 28 μM for pantothenate-7-amino-4-methylcoumarin (pantothenate-AMC), which was converted to pantothenic acid and AMC based on liquid chromatography-mass spectrometry (LC-MS) analysis. The assay also performed well in a 384-well microplate format under initial rate conditions (10% conversion) with a signal-to-background ratio (S/B) of 7 and a Z factor of 0.75. Preliminary screening of a library of 1280 pharmaceutically active compounds identified inhibitors with novel chemical scaffolds. This assay will be a powerful tool for target validation and drug lead identification and characterization.
Ruan, Benfang H.,Cole, Derek C.,Wu, Paul,Quazi, Amira,Page, Karen,Wright, Jill F.,Huang, Nelson,Stock, Joseph R.,Nocka, Karl,Aulabaugh, Ann,Krykbaev, Rustem,Fitz, Lori J.,Wolfman, Neil M.,Fleming, Margaret L.
p. 284 - 292
(2010)
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Purification and characterization of a cathepsin L-like enzyme from the body wall of the sea cucumber Stichopus japonicus
Cathepsin L-like enzyme was purified from the body wall of the sea cucumber Stichopus japonicus by an integral method involving ammonium sulfate precipitation and a series of column chromatographies on DEAE Sepharose CL-6B, Sephadex G-75, and TSK-GEL. The molecular mass of the purified enzyme was estimated to be 63 kDa by SDS-PAGE. The enzyme cleaved N-carbobenzoxy- phenylalanine-arginine 7-amido-4-methylcoumarin with Km (69.92 μM) and kcat (12.80/S) hardly hydrolyzed N-carbobenzoxy-arginine- arginine 7-amido-4-methylcoumarin and L-arginine 7-amido-4-methylcoumarin. The optimum pH and temperature for the purified enzyme were found to be 5.0 and 50°C. It showed thermal stability below 40°C. The activity was inhibited by sulfhydryl reagents and activated by reducing agents. These results suggest that the purified enzyme was a cathepsin L-like enzyme and that it existed in the form of its enzyme-inhibitor complex or precursor.
Zhu, Bei-Wei,Zhao, Lu-Lu,Sun, Li-Ming,Li, Dong-Mei,Murata, Yoshiyuki,Yu, Lei,Zhang, Lei
p. 1430 - 1437
(2008)
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New ambipolar blue emitting materials based on amino coumarin derivatives with high efficiency for organic lightemitting diodes
New blue emitting materials, 7-diphenylamino-4-methyl-coumarin (DPA-MC) and aminotri( 4-methylcoumarin) (T-MC) including coumarin moiety were synthesized by Ullman reaction. Optical and electronic properties were examined by UV-Vis. Absorption spectrum, PL spectrum, and cyclic voltammetry. UV-Vis. spectra of DPA-MC and T-MC in a film state showed maximum absorption wavelengths of 382 nm and 399 nm, respectively. PL spectra of DPA-MC and T-MC show maximum emission wavelengths of 463 nm and 481 nm respectively. Non-doped OLED devices were fabricated by using the synthesized materials as an emitting material layer. DPA-MC compound showed highly efficient luminescence properties. EL spectrum of DPA-MC exhibited a maximum value of 463 nm and DPA-MC device provided luminescence efficiency of 3.83 cd/A, power efficiency of 2.46 lm/W, external quantum efficiency of 3.71% and CIE coordinates of (0.154, 0.190) at a current density of 10 mA/cm2. In particular, Power efficiency increased by more than 1.6 times in DPA-MC (2.46 lm/W), which is higher than commercialized material, DPVBi (1.46 lm/W). High EL performance might come from ambipolar effects of a molecular structure. Copyright
Kim, Seungho,Lee, Kyung Jin,Kim, Beomjin,Lee, Jaehyun,Kay, Kwang-Yol,Park, Jongwook
p. 8020 - 8024
(2013)
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Polymersome Popping by Light-Induced Osmotic Shock under Temporal, Spatial, and Spectral Control
The light-triggered, programmable rupture of cell-sized vesicles is described, with particular emphasis on self-assembled polymersome capsules. The mechanism involves a hypotonic osmotic imbalance created by the accumulation of photogenerated species inside the lumen, which cannot be compensated owing to the low water permeability of the membrane. This simple and versatile mechanism can be adapted to a wealth of hydrosoluble molecules, which are either able to generate reactive oxygen species or undergo photocleavage. Ultimately, in a multi-compartmentalized and cell-like system, the possibility to selectively burst polymersomes with high specificity and temporal precision and to consequently deliver small encapsulated vesicles (both polymersomes and liposomes) is demonstrated.
Peyret, Ariane,Ibarboure, Emmanuel,Tron, Arnaud,Beauté, Louis,Rust, Ruben,Sandre, Olivier,McClenaghan, Nathan D.,Lecommandoux, Sebastien
p. 1566 - 1570
(2017)
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In Vivo Two-Photon Fluorescence Imaging of the Activity of the Inflammatory Biomarker LTA4H in a Mouse Pneumonia Model
Severe atmospheric haze caused by industrial pollution has severely affected human health and led to the increasing incidence of cardiopulmonary diseases, including pneumonia. Conventional methods for diagnosis of pneumonia are complicated and tedious, and current clinical imaging techniques might cause organ injuries to some extent. Therefore, an accurate, fast, and intact imaging method must be developed to diagnose pneumonia in the early stages. In this study, we propose a new two-photon fluorescence probe, named as ASPC, for detection of the activity of the inflammatory biomarker LTA4H through specific recognition and cleavage of amides containing the unnatural amino acid l-AspBzl. The activity of LTA4H in the lung tissues of mice was rapidly and accurately monitored for the first time and could be an indicator for diagnosis of pneumonia. The severity of pneumonia in mice caused by haze particulate was determined through imaging the activity of LTA4H as biomarker and confirmed using a commercial ELISA kit of interleukin-1β. This work provides a promising method for clinical detection of pneumonia and for screening specific depressors of LTA4H as potential drug candidates.
Wang, Hui,Xue, Ke,Li, Ping,Yang, Yuyun,He, Zixu,Zhang, Wei,Zhang, Wen,Tang, Bo
p. 6020 - 6027
(2018)
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Synthesis of Two Coumarin-Derived Schiff Bases and Investigation of theirs Selectivity for Zn2+
In this study, the coumarin-derived schiff bases (HL1 and HL2) have been designed and synthesized. Upon the addition of Zn2+, both of them show significant fluorescence enhancement owing to inhibits PET and ESIPT process respectively. However, the receptor HL2 response toward Cd2+, Mg2+, Ba2+, Ca2+ besides Zn2+ and exhibits fluorescence enhancement but not enough to detection of the concentration levels of Zn2+.
Fan, Long
p. 1331 - 1337
(2017)
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Purification and characterization of cathepsin L from the muscle of silver carp (Hypophthalmichthys molitrix)
Cathepsin L in silver carp musle was purified to 48.4-fold by acid-heat treatment and ammonium sulfate fractionation, followed by a series of chromatographic separations. The molecular mass of the purified enzyme was 30 kDa determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme was activated by dithiothreitol and cysteine while it was substantially inhibited by E-64 and insensitive to PMSF and pepstatin A, suggesting that the purified enzyme belongs to a family of cysteine proteinase. Consistent with this conclusion, Zn2+, Cu2+, Co 2+, Ni2+, and Fe2+ could strongly inhibit the activity of this enzyme. The optimal pH and temperature were 5.0 and 55°C, respectively. The enzyme catalyzed the hydrolysis of Z-Phe-Arg-MCA with a parameter of Km (8.27 μM) and Kcat (28.7 s-1) but hardly hydrolyzed Z-Arg-Arg-MCA, Arg-MCA, and Boc-Val-Leu-Lys-MCA. The microstructure analysis by scanning electron microscopy showed that this proteinase is capable of destroying the network structure of silver carp surimi gels. The enzyme exhibited a higher hydrolytic activity on surimi protein at 65°C than at 40°C.
Liu, Huan,Yin, Lijun,Zhang, Nan,Li, Shuhong,Ma, Changwei
p. 9584 - 9591
(2006)
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Application of 7-amino coumarins for the synthesis of novel and thermally stable water-insoluble azo-coumarin dyes
In this work, a series of novel azo-coumarin dyes were successfully synthesized by the diazotization of 7-amino coumarins followed by coupling with phenol derivatives. The diazotization and subsequent azo-coupling generated the related azo dyes at 0-5 °C in short reaction times with a simple experimental procedure. The spectral analysis of the resulted compounds was confirmed the proposed structures. By this development, the scope of heterocyclic compounds was increased.
Karami, Bahador,Kiani, Mahtab
p. 111 - 116
(2016)
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Effects of detergents on the West Nile virus protease activity
Detergents such as Triton X-100 are often used in drug discovery research to weed out small molecule promiscuous and non-specific inhibitors which act by aggregation in solution and undesirable precipitation in aqueous assay buffers. We evaluated the effe
Ezgimen, Manolya D.,Mueller, Niklaus H.,Teramoto, Tadahisa,Padmanabhan
p. 3278 - 3282
(2009)
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Effects of a high-pressure treatment on the activity and structure of rabbit muscle proteasome
The effects were assessed of high hydrostatic pressure on the activity and structure of rabbit skeletal muscle proteasome. The pressure effects on the activity were measured by the amount of fluorometric products released from synthetic substrates under pressure and from fluorescein isothiocyanate (FITC)-labeled casein after releasing the pressure. The effects on the structure were measured by fluorescene spectroscopy under pressure, and by circular dichroism (CD) spectroscopy and surface hydrophobicity after releasing the pressure. The optimal pressure for the hydrolyzing activity of synthetic peptides was 50 MPa. The degradation of FITC-labeled casein increased linearly with increasing pressure applied up to 200 MPa, and then markedly decreased up to at 400 MPa. The changes in the tertiary structure detected by fluorometric measurement were irreversible, whereas the changes in the secondary structure were small compared with those by heat treatment. The pressure-induced activation of proteasome therefore seems to have been due to a little unfolding of the active sites of proteasome.
Yamamoto, Shuhei,Otsuka, Yuichi,Borjigin, Gerelt,Masuda, Kanna,Ikeuchi, Yoshihide,Nishiumi, Tadayuki,Suzuki, Atsushi
p. 1239 - 1247
(2005)
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Microwave acceleration of the Pechmann reaction on graphite/montmorillonite K10: Application to the preparation of 4-substituted 7-aminocoumarins
Efficient synthesis of 7-aminocoumarins was performed via the Pechmann reaction by microwave irradiation of the reactants on solid support (graphite/montmorillonite K10). In this convenient new methodology, the strong thermal effect due to graphite/microwaves interaction is associated with the acidic catalyst role of the clay.
Frère, Stéphane,Thiéry, Valérie,Besson, Thierry
p. 2791 - 2794
(2001)
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Mechanistic Insights into the H2S-Mediated Reduction of Aryl Azides Commonly Used in H2S Detection
Hydrogen sulfide (H2S) is an important biological mediator and has been at the center of a rapidly expanding field focused on understanding the biogenesis and action of H2S as well as other sulfur-related species. Concomitant with this expansion has been the development of new chemical tools for H2S research. The use of H2S-selective fluorescent probes that function by H2S-mediated reduction of fluorogenic aryl azides has emerged as one of the most common methods for H2S detection. Despite this prevalence, the mechanism of this important reaction remains under-scrutinized. Here we present a combined experimental and computational investigation of this mechanism. We establish that HS-, rather than diprotic H2S, is the active species required for aryl azide reduction. The hydrosulfide anion functions as a one-electron reductant, resulting in the formation of polysulfide anions, such as HS2-, which were confirmed and trapped as organic polysulfides by benzyl chloride. The overall reaction is first-order in both azide and HS- under the investigated experimental conditions with ΔS? = -14(2) eu and ΔH? = 13.8(5) kcal/mol in buffered aqueous solution. By using NBu4SH as the sulfide source, we were able to observe a reaction intermediate (λmax = 473 nm), which we attribute to formation of an anionic azidothiol intermediate. Our mechanistic investigations support that this intermediate is attacked by HS- in the rate-limiting step of the reduction reaction. Complementing our experimental mechanistic investigations, we also performed DFT calculations at the B3LYP/6-31G(d,p), B3LYP/6-311++G(d,p), M06/TZVP, and M06/def2-TZVPD levels of theory applying the IEF-PCM water and MeCN solvation models, all of which support the experimentally determined reaction mechanism and provide cohesive mechanistic insights into H2S-mediated aryl azide reduction.
Henthorn, Hillary A.,Pluth, Michael D.
p. 15330 - 15336
(2015)
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Anti-AIDS agents 66: Syntheses and anti-HIV activity of phenolic and aza 3′,4′-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) derivatives
New phenolic and aza 3′,4′-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) analogs were synthesized and assayed for inhibition of HIV-1 IIIB replication in H9 lymphocytes. Compound 16, 4-methyl-1′-aza-DCK (4-methyl-aza-DCK), was less lipophilic than 4-methyl-DCK, and retained sub-micromolar anti-HIV activity with EC50 and TI values of 0.77 μM and >42, respectively. Moreover, it showed moderately improved metabolic stability. Introduction of phenolic hydroxyl groups to 4-methyl-DCK decreased lipophilicity significantly, but did not improve metabolic stability and also decreased activity.
Suzuki, Madoka,Yu, Donglei,Morris-Natschke, Susan L.,Smith, Philip C.,Lee, Kuo-Hsiung
p. 6852 - 6858
(2007)
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Capsosomes with "free-Floating" Liposomal Subcompartments
Capsosomes, that is, polymer capsules containing liposomal subcompartments, represent a promising new concept towards the design of artificial cells. Herein, capsosomes with control over the position of the subunits, "free-floating" in the capsule interior and/or associated with the polymer membrane, are reported. The functionality of these capsosomes is demonstrated via temperature-triggered encapsulated catalysis using subtilisin. Copyright
Hosta-Rigau, Leticia,Chung, Shiow Fong,Postma, Almar,Chandrawati, Rona,Staedler, Brigitte,Caruso, Frank
p. 4082 - 4087
(2011)
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O,o-Difluorination of aromatic azide yields a fast-response fluorescent probe for H2S detection and for improved bioorthogonal reactions
The development of efficient bioorthogonal reactions for sensing of endogenous biomolecules and for bioconjugation should be of paramount importance in the field of chemical biology. In this work, the o,o′-difluorinated aromatic azide was firstly employed to develop a new fast-response fluorescent probe 1 for H2S detection and for bioorthogonal reactions. Compared with non- and mono-fluorinated probes, 1 showed faster reaction toward H2S, the third gasotransmitter, in buffer (pH 7.4), implying that the reaction rate could be enhanced by the dual-fluorine groups. Furthermore, such enhanced reaction rates of 1 were also observed in the Staudinger reaction and strain-promoted azide-alkyne cycloaddition (SPAAC) based on the comparison studies of the non-fluorinated probe. Our results firstly highlight that the o,o′-difluorinated aromatic azide group should be useful for fast bioorthogonal reactions and H2S detection.
Zhang, Jie,Gao, Yasi,Kang, Xueying,Zhu, Zhentao,Wang, Zhiqian,Xi, Zhen,Yi, Long
p. 4212 - 4217
(2017)
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Chemical remodeling of cell-surface sialic acids through a palladium-triggered bioorthogonal elimination reaction
We herein report a chemical decaging strategy for the in situ generation of neuramic acid (Neu), a unique type of sialic acid, on live cells by the use of a palladium-mediated bioorthogonal elimination reaction. Palladium nanoparticles (Pd NPs) were found to be a highly efficient and biocompatible depropargylation catalyst for the direct conversion of metabolically incorporated N-(propargyloxycarbonyl)neuramic acid (Neu5Proc) into Neu on cell-surface glycans. This conversion chemically mimics the enzymatic de-N-acetylation of N-acetylneuramic acid (Neu5Ac), a proposed mechanism for the natural occurrence of Neu on cell-surface glycans. The bioorthogonal elimination was also exploited for the manipulation of cell-surface charge by unmasking the free amine at C5 to neutralize the negatively charged carboxyl group at C1 of sialic acids.
Wang, Jie,Cheng, Bo,Li, Jie,Zhang, Zhaoyue,Hong, Weiyao,Chen, Xing,Chen, Peng R.
p. 5364 - 5368
(2015)
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Photochemical reactions of azidocoumarins.
Photochemical reactions of 6-azidocoumarin and 7-azido-4-methylcoumarin in the presence of secondary amines have been investigated for their potential applications in photoaffinity labeling. It was found that the singlet nitrene generated from 6-azidocoumarin isomerized to a dehydroazepine intermediate that reacted with an amine to yield two isomeric adducts. Photolysis of 7-azido-4-methylcoumarin, in contrast, gave a triplet nitrene that abstracted hydrogen atoms from secondary amine molecules to form 7-amino-4-methylcoumarin as the major product. The difference in the intersystem crossing rate between the two compounds originates from the azido position relative to the carbonyl group. Because of its ability to form a covalent linkage with a nucleophile, 6-azidocoumarin is deemed to have a greater potential as a photoaffinity label than 7-azido-4-methylcoumarin.
Feng,Mahdavi-Anary,Partch,Li
p. 813 - 817
(1995)
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Coumarin-based turn-on fluorescence probes for highly selective detection of Pi in cell culture and Caenorhabditis elegans
Abstract Two coumarin-based fluorescence probes, 1 and 2, containing a methoxy oxalyl group as a reaction site were developed. These two novel probes displayed an instant turn-on fluorescence response specific towards Pi without interference from ATP and PPi. A selective 23-fold increase in fluorescence for 1 (in DMSO-HEPES) and a 20-fold increase for 2 (in DMSO) were observed. The proposed sensing mechanism for these compounds is Pi-triggered acetamide bond cleavage leading to release of the blue fluorophore coumarin, which was supported by 1H NMR and mass spectrometry data. Probe 1 was successfully used to image endogenous and exogenous Pi in living cells and to trace Pi released from ATP by apyrase in Caenorhabditis elegans.
Wang, Huan,Guo, Lin E.,Li, Xue Mei,Zhang, Li Mei,Xu, Qiu Lin,Wu, Gao Fen,Zhou, Ying,Zhang, Jun Feng
p. 293 - 298
(2015)
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Low molecular weight trypsin from hepatopancreas of freshwater prawn (Macrobrachium rosenbergii): Characteristics and biochemical properties
Trypsin was purified to homogeneity from hepatopancreas of freshwater prawn (HFWP) (Macrobrachium rosenbergii) using a series of chromatographies including Q-Sepharose, Superdex 75 and MonoQ columns. HFWP trypsin was purified 525-fold with a yield of 10.6%. Based on native-PAGE, the purified trypsin showed a single band. Trypsin had a molecular weight of 17 kDa as estimated by SDS-PAGE. The optimal pH and temperature for Boc-Val-Pro-Arg-MCA hydrolysis were 8.0 and 55 °C, respectively. Trypsin was stable to heat treatment up to 40 °C, and over a pH range of 7.0-11.0. Trypsin activity was strongly inhibited by soybean trypsin inhibitor, N-p-tosyl-L-lysine chloromethyl ketone (TLCK) and Pefabloc SC and was partially inhibited by ethylenediaminetetraacetic acid (EDTA). Apparent Km value of trypsin was 0.24 μM and K cat value was 607.56 s-1 for Boc-Val-Pro-Arg-MCA. The N-terminal amino acid sequence of 20 residues of HFWP trypsin was IVGGDEAAPGEFPHQISMQV, which was highly homologous with those from other species of prawn. HFWP trypsin also showed high collagenolytic activity toward prawn, shrimp and fish collagens, suggesting its possible role in muscle softening of freshwater prawn during extended storage.
Sriket, Chodsana,Benjakul, Soottawat,Visessanguan, Wonnop,Hara, Kenji,Yoshida, Asami,Liang, Xiao
p. 351 - 358
(2012)
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Identification of a member of the serralysin family isolated from a psychrotrophic bacterium, Pseudomonas fluorescens 114.
An extracellular metalloprotease named No. 114 protease is one of the major secretions of a psychrotrophic bacterium, Pseudomonas fluorescens 114, the cold-adaptation mechanism of which has not been identified. In this study, we purified and cloned No. 114 protease, which is a single polypeptide having a molecular mass of 47 kDa. This protease contains a zinc-binding motif (HEXXHXUGUXH: X, arbitrary amino acid; U, bulky hydrophobic amino acid), glycine-rich repeats (GGXGXD) and no cysteine residue, which are the features specifically found in serralysin subfamily. No. 114 protease has its maximum activity at the temperature of 35-40 degrees C, which is about 20 degrees C lower than that of a serralysin from a mesophilic bacterium, Pseudomonas aeruginosa. All these results imply that No. 114 protease from this psychrophilic bacterium is a unique member of the serralysin group characterized by a low optimal temperature.
Kumeta,Hoshino,Goda,Okayama,Shimada,Ohgiya,Matsuyama,Ishizaki
p. 1165 - 1170
(1999)
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Hydrolysis of dipeptide derivatives reveals the diversity in the M49 family
Dipeptidyl peptidase III, a metallopeptidase of the M49 family, was first identified (in the pituitary) by its specific cleavage of diarginyl arylamides, which have been used as preferred assay substrates until now. Here we examined the activity of the yeast and human dipeptidyl peptidase III in parallel. The human enzyme preferred Arg2-β-naphthylamide and showed 620-fold higher kcat/Km for this substrate. In contrast, the yeast enzyme did not display a preference for any of the X-Arg-β-naphthylamide analyzed. The replacement of Gly505 with Asp, resulted in a less active, but more selective, yeast enzyme form. These results indicate diversity in cleavage specificity in the M49 family.
Jajcanin-Jozic, Nina,Abramic, Marija
p. 767 - 771
(2013)
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β-Alanyl aminopeptidase-activated fluorogenic probes for the rapid identification of Pseudomonas aeruginosa in clinical samples
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.
p. 58884 - 58889
(2016)
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Masked Amino Trimethyl Lock (H2N-TML) Systems: New Molecular Entities for the Development of Turn-On Fluorophores and Their Application in Hydrogen Sulfide (H2S) Imaging in Human Cells
Masked trimethyl lock (TML) systems as molecular moieties enabling the bioresponsive release of compounds or dyes in a controlled temporal and spatial manner have been widely applied for the development of drug conjugates, prodrugs or molecular imaging tools. Herein, we report the development of a novel amino trimethyl lock (H2N-TML) system as an auto-immolative molecular entity for the release of fluorophores. We designed Cou-TML-N3 and MURh-TML-N3, two azide-masked turn-on fluorophores. The latter was demonstrated to selectively release fluorescent MURh in the presence of physiological concentrations of the redox-signaling molecule H2S in vitro and was successfully applied to image H2S in human cells.
Jimidar, Claire Cheyenne,Grunenberg, J?rg,Karge, Bianka,Fuchs, Hazel Leanne Sarah,Br?nstrup, Mark,Klahn, Philipp
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(2021/11/10)

Switching on prodrugs using radiotherapy
Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept of a chemistry-based strategy, whereby gamma/X-ray irradiation mediates the activation of a cancer prodrug, thereby enabling simultaneous chemo-radiotherapy with radiotherapy locally activating a prodrug. In an initial demonstration, we show the activation of a fluorescent probe using this approach. Expanding on this, we show how sulfonyl azide- and phenyl azide-caged prodrugs of pazopanib and doxorubicin can be liberated using clinically relevant doses of ionizing radiation. This strategy is different to conventional chemo-radiotherapy radiation, where chemo-sensitization of the cancer takes place so that subsequent radiotherapy is more effective. This approach could enable site-directed chemotherapy, rather than systemic chemotherapy, with ‘real time’ drug decaging at the tumour site. As such, it opens up a new era in targeted and directed chemotherapy. [Figure not available: see fulltext.].
Geng, Jin,Zhang, Yichuan,Gao, Quan,Neumann, Kevin,Dong, Hua,Porter, Hamish,Potter, Mark,Ren, Hua,Argyle, David,Bradley, Mark
p. 805 - 810
(2021/06/14)

Generation of H2S from Thiol-Dependent NO Reactivity of Model [4Fe-4S] Cluster and Roussin's Black Anion
Iron-sulfur clusters (Fe-S) have been well established as a target for nitric oxide (NO) in biological systems. Complementary to protein-bound studies, synthetic models have provided a platform to study what iron nitrosylated products and byproducts are produced depending on a controlled reaction environment. We have previously shown a model [2Fe-2S] system that produced a dinitrosyl iron complex (DNIC) upon nitrosylation along with hydrogen sulfide (H2S), another important gasotransmitter, in the presence of thiol, and hypothesized a similar reactivity pattern with [4Fe-4S] clusters which have largely produced inconsistent reaction products across biological and synthetic systems. Roussin's black anion (RBA), [Fe4(μ3-S)3(NO)7]-, is a previously established reaction product from synthetic [4Fe-4S] clusters with NO. Here, we present a new reactivity for the nitrosylation of a synthetic [4Fe-4S] cluster in the presence of thiol and thiolate. [Et4N]2[Fe4S4(SPh)4] (1) was nitrosylated in the presence of excess PhSH to generate H2S and an "RBA-like"intermediate that when further reacted with [NEt4][SPh] produced a {Fe(NO)2}9 DNIC, [Et4N][Fe(NO)2(SPh)2] (2). This "RBA-like"intermediate proved difficult to isolate but shares striking similarities to RBA in the presence of thiol based on IR υ(NO) stretching frequencies. Surprisingly, the same reaction products were produced when the reaction started with RBA and thiol. Similar to 1/NO, RBA in the presence of thiol and thiolate generates stoichiometric amounts of DNIC while releasing its bridging sulfides as H2S. These results suggest not only that RBA may not be the final product of [4Fe-4S] + NO but also that RBA has unprecedented reactivity with thiols and thiolates which may explain current challenges around identifying biological nitrosylated Fe-S clusters.
Oakley, Kady M.,Zhao, Ziyi,Lehane, Ryan L.,Ma, Ji,Kim, Eunsuk
p. 15910 - 15917
(2021/07/20)

Hydrogen sulfide donor Preparation method and application thereof
The invention relates to a hydrogen sulfide donor, a preparation method and application thereof, and belongs to the technical field of molecular biology. The invention provides a hydrogen sulfide donor which has the structure represented by the following general formula I, wherein R is - NCS, OOOOOCCH is CH2 . One of the following. The hydrogen sulfide donor provided by the invention has the advantages of single release path, high release efficiency and the like, and can also realize visualization of hydrogen sulfide release through near-infrared fluorescence response.
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Paragraph 0038

(2021/10/11)

B(C6F5)3-catalyzed synthesis of coumarins via Pechmann condensation under solvent-free conditions
Tris(pentafluorophenyl)borane [B(C6F5)3] catalyzed simple, efficient and environmentally benign protocol has been developed for the Pechmann condensation using variety of phenols and β-ketoesters under solvent-free conditions to afford coumarin derivatives. The present protocol displayed significant advantages such as low catalyst loading, short reaction time, mild reaction conditions, low toxicity, easy work-up, high yields, and compatibility with other functional groups. In addition, it is a convenient, clean, and fast alternative approach for synthesizing variety of coumarin derivatives. Moreover, the applicability of this method towards large-scale synthesis demonstrated its suitability for the industrial application. Graphic abstract: [Figure not available: see fulltext.]
Prajapti, Santosh Kumar,Rao, S. Prakash
p. 469 - 473
(2021/03/26)

On-Demand Activation of a Bioorthogonal Prodrug of SN-38 with Fast Reaction Kinetics and High Releasing Efficiency in Vivo
Although a myriad of bioorthogonal prodrugs have been developed, very few of them present both fast reaction kinetics and complete cleavage. Herein, we report a new bioorthogonal prodrug strategy with both fast reaction kinetics (k2: ～103 M-1 s-1) and complete cleavage (>90% within minutes) using the bioorthogonal reaction pair of N-oxide and boron reagent. Distinctively, an innovative 1,6-elimination-based self-immolative linker is masked by N-oxide, which can be bioorthogonally demasked by a boron reagent for the release of both amino and hydroxy-containing payload in live cells. Such a strategy was applied to prepare a bioorthogonal prodrug for a camptothecin derivative, SN-38, resulting in 10-fold weakened cytotoxicity against A549 cells, 300-fold enhanced water solubility, and on-demand activation upon a click reaction both in vitro and in vivo. This novel bioorthogonal prodrug strategy presents significant advances over the existing ones and may find wide applications in drug delivery in the future.
Feng, Shun,Ji, Xingyue,Long, Ya-Qiu,Zhou, Jujun,Zhou, Zhou
(2022/01/14)

Enzyme Catalysis in Non-Native Environment with Unnatural Selectivity Using Polymeric Nanoreactors
The utilization of enzymes for catalysis in organic solvents, while exhibiting selectivity to different substrates, is a big challenge. We report an amphiphilic random copolymer system that self-assembles with enzymes in an organic solvent to form nanoreactors. These encapsulated enzymes are not denatured and they do preserve the catalytic activity. The cross-linkable functional groups in the hydrophobic compartments of the polymers offer to control accessibility to the enzyme. This varied accessibility due to the polymer host, rather than the enzyme itself, endows the nanoreactor with an unnatural selectivity. The findings here highlight the significant potential of simple polymer-based enzyme nanoreactors to execute selective organic reactions under non-native conditions.
Gao, Jingjing,Le, Stephanie,Thayumanavan, S.
supporting information
p. 27189 - 27194
(2021/11/18)

Prostate-Specific Membrane Antigen-Targeted Turn-on Probe for Imaging Cargo Release in Prostate Cancer Cells
The tunable nature of phosphoramidate linkers enables broad applicability as pH-triggered controlled-release platforms, particularly in the context of antibody-and small-molecule-drug conjugates (ADCs and SMDCs), where there remains a need for new linker technology. Herein, we explored in-depth the release of turn-on fluorogenic payloads from a homoserinyl-based phosphoramidate acid-cleavable linker. Kinetics of payload release from the scaffold was observed in buffers representing the pH conditions of systemic circulation, early and late endosomes, and lysosomes. It was found that payload release takes place in two key consecutive steps: (1) P-N bond hydrolysis and (2) spacer immolation. These two steps were found to follow pseudo-first-order kinetics and had opposite dependencies on pH. P-N bond hydrolysis increased with decreasing pH, while spacer immolation was most rapid at physiological pH. Despite the contrasting release kinetics of these two steps, maximal payload release was observed at the mildly acidic pH (5.0-5.5), while minimal payload release occurred at physiological pH. We integrated this phosphoramidate-payload linker system into a PSMA-targeted fluorescent turn-on probe to study the intracellular trafficking and release of a fluorescent payload in PSMA-expressing prostate cancer cells. Results showed excellent turn-on and accumulation of the coumarin payload in the late endosomal and lysosomal compartments of these cells. The release properties of this linker mark it as an attractive alternative in the modular design of ADCs and SMDCs, which demand selective intracellular payload release triggered by the pH changes that accompany intracellular trafficking.
Abbasi, Armina,Berkman, Clifford E.,Caromile, Leslie A.,Lovingier, Christine L.,Mesbahi, Nooshin,Olatunji, Feyisola P.,Panteah, Mylan,Savoy, Emily A.,Talley, Cresencia M.
p. 2386 - 2396
(2021/11/16)

PYROPTOSIS-INDUCED IMMUNOTHERAPY
Pyroptosis-induced immunotherapy is effected by activating a pore-forming, pyrpotogenic molecule, wherein the activating induces tumor cell pryoptosis and causes tumor regression by T-cell mediated anti-tumor immunity.
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Paragraph 032; 077-078

(2021/03/05)

Coumarins by Direct Annulation: β-Borylacrylates as Ambiphilic C3-Synthons
Modular β-borylacrylates have been validated as programmable, ambiphilic C3-synthons in the cascade annulation of 2-halo-phenol derivatives to generate structurally and electronically diverse coumarins. Key to this [3+3] disconnection is the BPin unit which serves a dual purpose as both a traceless linker for C(sp2)–C(sp2) coupling, and as a chromophore extension to enable inversion of the alkene geometry via selective energy transfer catalysis. Mild isomerisation is a pre-condition to access 3-substituted coumarins and provides a handle for divergence. The method is showcased in the synthesis of representative natural products that contain this venerable chemotype. Facile entry into π-expanded estrone derivatives modified at the A-ring is disclosed to demonstrate the potential of the method in bioassay development or in drug repurposing.
Wienhold, Max,Molloy, John J.,Daniliuc, Constantin G.,Gilmour, Ryan
p. 685 - 689
(2020/11/30)

Harnessing Endogenous Formate for Antibacterial Prodrug Activation by in cellulo Ruthenium-Mediated Transfer Hydrogenation Reaction
The abundance and evolving pathogenic behavior of bacterial microorganisms give rise to antibiotic tolerance and resistance which pose a danger to global public health. New therapeutic strategies are needed to keep pace with this growing threat. We propose a novel approach for targeting bacteria by harnessing formate, a cell metabolite found only in particular bacterial species, to activate an antibacterial prodrug and selectively inhibit their growth. This strategy is premised on transfer hydrogenation reaction on a biorthogonal substrate utilizing native formate as the hydride source as a means of uncaging an antibacterial prodrug. Using coordination-directed 3-component assembly to prepare a library of 768 unique Ru–Arene Schiff-base complexes, we identified several candidates that efficiently reduced sulfonyl azide functional group in the presence of formate. This strategy paves the way for a new approach of targeted antibacterial therapy by exploiting unique bacterial metabolites.
Ang, Wee Han,Shen, Linghui,Weng, Cheng
supporting information
p. 9314 - 9318
(2020/04/29)

Coumarin Schiff base derivative as well as preparation method and application thereof
The invention relates to a coumarin Schiff base derivative as well as a preparation method and application thereof, belonging to the technical field of metal ion detection. The coumarin Schiff base compound is 2-hydroxyl Schiff base-4-methylcoumarin. The specific structural formula of the coumarin Schiff base derivative is as shown in the specification. The invention further relates to a preparation method and application of the coumarin Schiff base derivative. The coumarin Schiff base derivative is high in Cr selectivity and Cr sensitivity, high in binding capacity and beneficial forCr detection.
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Paragraph 0022; 0053; 0059-0084

(2020/11/25)

Multiplex Optical Urinalysis for Early Detection of Drug-Induced Kidney Injury
Drug-induced kidney injury (DIKI) is a significant contributor of both acute and chronic kidney injury and remains a major concern in drug development and clinical care. However, current clinical diagnostic methods often fail to accurately and timely detect nephrotoxicity. This study reports the development of activatable molecular urinary reporters (MURs) that are able to specifically detect urinary biomarkers including γ-glutamyl transferase (GGT), alanine aminopeptidase (AAP), and N-acetyl-β-d-glucosaminidase (NAG). By virtue of their discrete absorption and emission properties, the mixture of MURs can serve as a cocktail sensor for multiplex optical urinalysis in the mouse models of drug-induced acute kidney injury (AKI) and chronic kidney disease (CKD). The MURs cocktail not only detects nephrotoxicity earlier than the tested clinical diagnostic methods in drug-induced AKI and CKD mice models, but also possesses a higher diagnostic accuracy. Therefore, MURs hold great promise for detection of kidney function in both preclinical drug screening and clinical settings.
Cheng, Penghui,Huang, Jiaguo,Li, Jingchao,Miao, Qingqing,Pu, Kanyi
p. 6166 - 6172
(2020/05/19)

Mutations of key substrate binding residues of leishmanial peptidase T alter its functional and structural dynamics
Background: M20 aminopeptidases, such as Peptidase T (PepT), are implicated in the hydrolysis of oligopeptides during the terminal stages of protein degradation pathway to maintain turnover. Therefore, specific inhibition of PepT bores well for the development of novel next-generation antileishmanials. This work describes the metal dependence, substrate preferences and inhibition of PepT, and demonstrates in detail the role of its two conserved substrate binding residues. Methods: PepT was purified and characterized using a scheme of peptide substrates and peptidomimetic inhibitors. Residues T364 and N378 were mutated and characterized with an array of biochemical, biophysical and structural biology methods. Results: PepT sequence carries conserved motifs typical of M20 peptidases and our work on its biochemistry shows that this cytosolic enzyme carries broad substrate specificity with best cleavage preference for peptides carrying alanine at the P1 position. Peptidomimetics amastatin and actinonin occupied S1 pocket by competing with the substrate for binding to active site and inhibited PepT potently, while arphamenine A and bestatin were less effective inhibitors. We further show that the mutation of conserved substrate binding residues (T364 and N378) to alanine affects structure, reduces substrate binding and alters the amidolytic activity of this dimeric enzyme. Conclusions: PepT preferentially hydrolyzes oligopeptides carrying alanine at P1 position and is potently inhibited by peptidomimetics. Reduced substrate binding after mutations was a key factor involved in amidolytic digressions. General significance: This study provides insights for further exploration of the druggability of PepT and highlights prospective applications of this enzyme along with its mutazyme T364A/N378A.
Bhat, Saleem Yousuf,Qureshi, Insaf Ahmed
(2019/11/11)

Evaluation of thioamides, thiolactams and thioureas as hydrogen sulfide (H2S)donors for lowering blood pressure
Hydrogen sulfide (H2S)is a biologically important gaseous molecule that exhibits promising protective effects against a variety of pathological processes. For example, it was recognized as a blood pressure lowering agent. Aligned with the need for easily modifiable platforms for the H2S supply, we report here the preparation and the H2S release kinetics from a series of structurally diversified thioamides, thiolactams and thioureas. Three different thionation methods based on the usage of a phosphorus pentasulfide and Lawesson reagent were applied to prepare the target thioamides and thiolactams. Furthermore, obtained H2S donors were evaluated both in in vivo and in vitro studies. The kinetic parameters of the liberating H2S was determined and compared with NaHS and GYY4137 using two different detection technics i.e.; fluorescence labeling 7-azido-4-methyl-2H-chromen-2-one and 5,5‘-dithiobis (2-nitrobenzoic acid), sulfhydryl probe, also known as the Ellman's reagent. We have proved that the amount of releasing H2S from these compounds is controllable through structural modifications. Finally, the present study shows a hypotensive response to an intravenous administration of the developed donors in the anesthetized rats.
Zaorska, Ewelina,Hutsch, Tomasz,Gawry?-Kopczyńska, Marta,Ostaszewski, Ryszard,Ufnal, Marcin,Koszelewski, Dominik
supporting information

(2019/04/29)

Evaluation of novel coumarin-proline sulfonamide hybrids as anticancer and antidiabetic agents
Cancer and diabetes are considered as two major diseases affecting human health worldwide. Various therapies are available for treatment of cancer and diabetes individually, peptide linkage containing proline sulfonamide can be a promising therapy for treatment of both cancer as well as diabetes. Here, we report design and synthesis of novel coumarin-proline sulfonamide derivatives as anticancer and antidiabetic agents. All the synthesized compounds were screened for their anticancer activity against lungs cancer cell line (A549) and breast cancer cell line (MCF7) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye (MTT)assay and antidiabetic activity using DPP-IV inhibition assay. Compound 16b showed excellent activity against breast cancer cell line (MCF7) with IC50 value of 1.07 μM. All compounds showed moderate DPP-IV inhibition.
Durgapal, Sunil Dutt,Soman, Shubhangi S.
supporting information
p. 2869 - 2883
(2019/08/22)

Coumarin oxime ester photoinitiator
The invention provides a coumarin oxime ester photoinitiator and a preparation method thereof. The molecular structure general formula is shown in the formula (I). The photoinitiator triggers photocuring under the radiation wavelength of 360-450 nm, and is applied to the fields such as single-photon 3D printing, double-photon 3D printing, printing ink and photoresist. The photoinitiator can serveas an LED photoinitiator and a double-photon photoinitiator, good triggering activity is achieved, one photoinitiator has two purposes, and the manufacturing cost is reduced to a certain degree.
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Paragraph 0068-0074

(2019/10/02)

Copper-Triggered Bioorthogonal Cleavage Reactions for Reversible Protein and Cell Surface Modifications
Temporal and reversible control over protein and cell conjugations holds great potential for traceless release of antibody-drug conjugates (ADCs) on tumor sites as well as on-demand altering or removal of targeting elements on cell surface. We herein developed a bioorthogonal and traceless releasable reaction on proteins and intact cells to fulfill such purposes. A systematic survey of transition metals in catalyzing the bioorthogonal cleavage reactions revealed that copper complexes such as Cu(I)-BTTAA and dual-substituted propargyl (dsPra) or propargyloxycarbonyl (dsProc) moieties offered a bioorthogonal releasable pair for reversible blockage and rescue of primary amines and phenol alcohols on small molecule drugs, protein side chains, as well as intact cell surface. For proof-of-concept, we employed such Cu(I)-BTTAA/dsProc and Cu(I)-BTTAA/dsPra pairs as a "traceless linker" strategy to construct cleavable ADCs to unleash cytotoxic compounds on cancer cells in situ and as a "reversible modification" strategy for cell surface engineering. Furthermore, by coupling with the genetic code expansion strategy, we site-specifically modulated ligand-receptor interactions on live cell membranes. Together, our work expanded the transition-metal-mediated bioorthogonal cleavage tool kit from terminal decaging to internal-linker breakage, which offered a temporal and reversible conjugation strategy on therapeutic proteins and cells.
Wang, Xin,Liu, Yanjun,Fan, Xinyuan,Wang, Jie,Ngai, William Shu Ching,Zhang, Heng,Li, Jiaofeng,Zhang, Gong,Lin, Jian,Chen, Peng R.
p. 17133 - 17141
(2019/11/03)

"Close-to-Release": Spontaneous Bioorthogonal Uncaging Resulting from Ring-Closing Metathesis
Bioorthogonal uncaging reactions offer versatile tools in chemical biology. In recent years, reactions have been developed to proceed efficiently under physiological conditions. We present herein an uncaging reaction that results from ring-closing metathesis (RCM). A caged molecule, tethered to a diolefinic substrate, is released via spontaneous 1,4-elimination following RCM. Using this strategy, which we term "close-to-release", we show that drugs and fluorescent probes are uncaged with fast rates, including in the presence of mammalian cells or in the periplasm of Escherichia coli. We envision that this tool may find applications in chemical biology, bioengineering and medicine.
Sabatino, Valerio,Rebelein, Johannes G.,Ward, Thomas R.
p. 17048 - 17052
(2019/10/11)

Design and synthesis of aminocoumarin derivatives as DPP-IV inhibitors and anticancer agents
DPP-IV “a moonlighting protein” has immerged as promising pathway to control Type 2 diabetes as well as found to play key role in earlier stages of cancer. Here we have reported design, synthesis and applications of aminocoumarin derivatives as DPP-IV inhibitors. Compounds have been synthesized and studied for their DPP-IV inhibition activity. Three compounds have shown moderate inhibition at 100 μM concentration. All compounds were also screened for their anticancer activity against A549 (Lung cancer cell line), MCF-7 (Breast cancer cell line) using MTT assay. One of the compounds has shown very good anticancer activity with IC50 value 24 ± 0.1 nM against A549 cell line.
Soni, Rina,Soman, Shubhangi S.
p. 277 - 284
(2018/05/24)

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)

Hydrogen as a Bio-Orthogonal Trigger for Spatiotemporally Controlled Caged Prodrug Activation
The use of a p-nitrobenzyloxycarbonyl (pNZ) protecting group on the FDA-approved lung cancer drug gemcitabine affords a caged drug with very low in vitro toxicity in a human model cell line (A549). To activate this type of caged potent drug, simultaneous presence of two items is needed: platinum nanoparticles and hydrogen-containing gas mixtures. This combination may later allow a more precise and controlled local delivery of highly potent cytostatic compounds, and may eventually permit reduction of the severe side effects of such chemotherapy treatments. Hydrogen, though an unusual medical agent, is well tolerated, and here used mixtures are derived from diving (deep diving gas). Pt nanoparticles at here used concentrations may eventually be locally deposited into the lungs through minimal invasive inhalation. We demonstrate the use of hydrogen as an on/off uncaging switch and show repeated use of the Pt nanoparticles for a series of uncaging events.
Herzog, Antoine F.,Schneider, Elia M.,Stark, Wendelin J.
(2018/11/10)

Bottom-Up Construction of an Adaptive Enzymatic Reaction Network
The reproduction of emergent behaviors in nature using reaction networks is an important objective in synthetic biology and systems chemistry. Herein, the first experimental realization of an enzymatic reaction network capable of an adaptive response is reported. The design is based on the dual activity of trypsin, which activates chymotrypsin while at the same time generating a fluorescent output from a fluorogenic substrate. Once activated, chymotrypsin counteracts the trypsin output by competing for the fluorogenic substrate and producing a non-fluorescent output. It is demonstrated that this network produces a transient fluorescent output under out-of-equilibrium conditions while the input signal persists. Importantly, in agreement with mathematical simulations, we show that optimization of the pulse-like response is an inherent trade-off between maximum amplitude and lowest residual fluorescence.
Helwig, Britta,van Sluijs, Bob,Pogodaev, Aleksandr A.,Postma, Sjoerd G. J.,Huck, Wilhelm T. S.
supporting information
p. 14065 - 14069
(2018/10/09)

A cell-penetrating artificial metalloenzyme regulates a gene switch in a designer mammalian cell
Complementing enzymes in their native environment with either homogeneous or heterogeneous catalysts is challenging due to the sea of functionalities present within a cell. To supplement these efforts, artificial metalloenzymes are drawing attention as they combine attractive features of both homogeneous catalysts and enzymes. Herein we show that such hybrid catalysts consisting of a metal cofactor, a cell-penetrating module, and a protein scaffold are taken up into HEK-293T cells where they catalyze the uncaging of a hormone. This bioorthogonal reaction causes the upregulation of a gene circuit, which in turn leads to the expression of a nanoluc-luciferase. Relying on the biotin-streptavidin technology, variation of the biotinylated ruthenium complex: the biotinylated cell-penetrating poly(disulfide) ratio can be combined with point mutations on streptavidin to optimize the catalytic uncaging of an allyl-carbamate-protected thyroid hormone triiodothyronine. These results demonstrate that artificial metalloenzymes offer highly modular tools to perform bioorthogonal catalysis in live HEK cells.
Okamoto, Yasunori,Kojima, Ryosuke,Schwizer, Fabian,Bartolami, Eline,Heinisch, Tillmann,Matile, Stefan,Fussenegger, Martin,Ward, Thomas R.
(2018/05/24)

The identification of inhibitory compounds of Rickettsia prowazekii methionine aminopeptidase for antibacterial applications
Methionine aminopeptidase (MetAP) is a dinuclear metalloprotease responsible for the cleavage of methionine initiator residues from nascent proteins. MetAP activity is necessary for bacterial proliferation and is therefore a projected novel antibacterial
Helgren, Travis R.,Seven, Elif S.,Chen, Congling,Edwards, Thomas E.,Staker, Bart L.,Abendroth, Jan,Myler, Peter J.,Horn, James R.,Hagen, Timothy J.
p. 1376 - 1380
(2018/04/11)

A thioether-directed palladium-cleavable linker for targeted bioorthogonal drug decaging
We describe the development of a bifunctional linker that simultaneously allows site-specific protein modification and palladium-mediated bioorthogonal decaging. This was enabled by a thioether binding motif in the propargyl carbamate linker and a readily available palladium complex. We demonstrate the efficiency of this reaction by controlled drug release from a PEGylated doxorubicin prodrug in cancer cells. The linker can be easily installed into cysteine bearing proteins which we demonstrated for the construction of an anti-HER2 nanobody-drug conjugate. Targeted delivery of the nanobody drug conjugate showed effective cell killing in HER2+ cells upon palladium-mediated decaging.
Stenton, Benjamin J.,Oliveira, Bruno L.,Matos, Maria J.,Sinatra, Laura,Bernardes, Gon?alo J. L.
p. 4185 - 4189
(2018/05/22)

Nanosilica molybdic acid: synthesis, characterization and application as a green and reusable catalyst for the Pechmann condensation
Abstract: Nanosilica molybdic acid (SMA NPs) was founded as an efficient and recyclable nanocatalyst for the synthesis of coumarin derivatives in excellent yields with good purity. Nano-SMA as a new solid acid was characterized by X-ray fluorescence, X-ray diffraction, energy-dispersive X-ray analyzer, transmission electron microscopy and Fourier transform infrared spectroscopy. Coumarin derivatives were obtained via the Pechmann condensation reaction of phenols and β-ketoesters at 80?°C under solvent-free conditions. The main advantages of the present procedure are high yields, shorter reaction time and green chemistry procedure, simple work-up and inexpensive and reusability of the catalyst. Graphical Abstract: [Figure not available: see fulltext.]
Kiani, Mahtab,Karami, Bahador
p. 655 - 663
(2017/01/17)

Preparation of a novel, efficient, and recyclable magnetic catalyst, γ-Fe2O3@HAp-Ag nanoparticles, and a solvent- and halogen-free protocol for the synthesis of coumarin derivatives
In this protocol, Ag supported on the hydroxyapatite-core–shell magnetic γ-Fe2O3nanoparticles (γ-Fe2O3@HAp-Ag NPs) as a novel, efficient, and magnetically recyclable catalyst is synthesized, and characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and vibrating sample magnetometry (VSM). The use of the catalyst is described in the synthesis of coumarin derivatives by the Pechmann condensation of various phenols with β-ketoesters under solvent- and halogen-free conditions at 80?°C. This novel and inexpensive method offers advantages, such as recyclability simple experimental protocol, short reaction time, minimal work-up procedure, and excellent yields of products, together with desirable, eco-friendly, green aspects by avoiding toxic elements and solvents, and ease of recovery from the reaction mixture using an external magnet.
Abbasi, Zahra,Rezayati, Sobhan,Bagheri, Maryam,Hajinasiri, Rahimeh
p. 75 - 82
(2017/01/13)

Synthesis and Bioassay of Novel Substituted Pyrano[2,3-f]cinnoline-2-ones
A new series of 9-substituted-4,10-dimethylpyrano[2,3-f]cinnolin-2-ones (5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5l, 5m) were synthesized via intramolecular cyclization of the respective acyl amidrazone derivatives (4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 4k, 4l, 4m), catalyzed by polyphosphoric acid. Compounds (4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 4k, 4l, 4m) were synthesized through direct interaction of coumarin-7-yl hydrazonoyl chloride (3) with the corresponding cyclic sec-amines in the presence of triethylamine. The structures of the new compounds were confirmed by elemental analyses, NMR, and MS spectral data. The antitumor activity of compounds 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5l, 5m was evaluated in vitro on breast cancer cell line (MCF-7) by a cell viability assay utilizing the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Among the compounds tested, compounds 5d, 5f, 5k, and 5h showed potential anti-MCF-7 activity and were able to reduce the viability after 72 h to less than 50%.
Al-zagameem, Abla S.,El-Abadelah, Mustafa M.,Zihlif, Malek A.,Naffa, Randa G.,Al-Smadi, Musa L.,Mubarak, Mohammad S.
p. 1771 - 1777
(2016/11/23)

One-pot synthesis of coumarine derivatives using butylenebispyridinium hydrogen sulfate as novel ionic liquid catalyst
Pechmann condensation reaction of 3-hydroxyphenol and ethyl acetoacetate in the presence of 1,1′‐butylenebispyridinium hydrogen sulfate as an efficient, green, and recyclable catalyst produces 7-hydroxy-4-methylcoumarin in good yield under solvent-free conditions at room temperature. This catalyst has advantages such as the following: good to excellent yields, short reaction times, simplicity in operation, and easy workup procedure.
Rezayati, Sobhan,Sheikholeslami-Farahani, Fatemeh,Rostami-Charati, Faramarz,Abad, Saeid Afshari Sharif
p. 4097 - 4107
(2016/07/06)

Meglumine sulfate catalyzed solvent-free one-pot synthesis of coumarins under microwave and thermal conditions
A convenient method has been developed for the Pechmann reaction of phenols and β-keto esters catalyzed by meglumine sulfate. Solvent-free conditions, inexpensive catalyst, short reaction times, high yield, and ease of purification of the products are the advantages of this protocol. This novel catalytic system is expected to contribute to the development of more benign Pechmann condensation reactions of phenols with β-keto esters.
Moradi, Leila,Rabiei, Khadijeh,Belali, Fateme
supporting information
p. 1283 - 1291
(2016/08/16)

Sulfonated core-shell magnetic nanoparticle (Fe3O4@SiO2@PrSO3H) as a highly active and durable protonic acid catalyst; Synthesis of coumarin derivatives through pechmann reaction
Sulfonic acid supported silica coated magnetic nanoparticles (Fe3O4@SiO2@PrSO3H), was prepared by using low cost precursors and a facile immobilization technique. The final catalyst, which was characterized by XRD, FT-IR, vibrating sample magnetometer (VSM), TEM, and TGA techniques, was found to be an efficient and environmentally benign solid acid for the Pechmann condensation of substituted phenols with ethyl acetoacetate leading to the formation of coumarin derivatives. After the reaction, the catalyst could be effortlessly separated by external magnet and reused for 22 consecutive runs, without any significant loss in catalytic efficiency. The catalytic system presented offers a reusable strategy for the efficient synthesis of coumarin, simplicity in operation, and a green reaction profile by avoiding toxic conventional catalysts and solvents. Green earth and blue sky: Herein, we wish to disclose a simple bench top procedure for the synthesis of sulfonated core-shell magnetic nanoparticles (SMNPs) (Fe3O4@SiO2@PrSO3H) and discuss its performance as a very strong solid acid in the Pechmann condensation reaction.
Esfahani, Farhad Kabiri,Zareyee, Daryoush,Yousefi, Reza
p. 3333 - 3337
(2015/04/16)

Environmentally sustainable magnetic solid sulfonic acid: An efficient and reusable catalyst for the Pechmann reaction
Abstract An environmentally benign sulfonic acid nanocomposite based on Fe3O4@SiO2 core-shell magnetic nanoparticles, Fe3O4@SiO2@Et-PhSO3H, was prepared and the acidity and utility of the catalyst were explored for the synthesis of a diverse range of coumarin derivatives under solvent-free conditions. The catalyst shows potential for scale up in the synthesis of coumarins with high purity and was easily separated by using an external magnet. The recovered catalyst was reused in seven cycles without any significant loss of activity.
Mobaraki, Akbar,Yasham, Shahriar,Movassagh, Barahman
supporting information
p. 1263 - 1268
(2015/06/02)

Synthesis of the coumarins via pechmann method in the presence of environmentally friendly Y(NO3)3×6H2O
Several substituted coumarins can be prepared in high yield and purity by direct reaction of β-keto esters and phenol derivatives in the presence of a catalytic amount Y(NO3)3×6H2O as Lewis acid and at ambient temperature under solvent-free conditions. Several substituted coumarins can be prepared in high yield and purity by direct reaction of β-keto esters and phenol derivatives in the presence of a catalytic amount Y(NO3)3×6H2O as Lewis acid and at ambient temperature under solvent-free conditions. This method that is based on Pechmann condensation is very easy and rapid reaction for the synthesis of coumarin derivatives. Copyright
Karami, Bahador,Kiani, Mahtab
p. 213 - 216
(2014/05/06)

Recyclable CMK-5 supported sulfonic acid as an environmentally benign catalyst for solvent-free one-pot construction of coumarin through Pechmann condensation
Sulfonic acid modified nanostructured CMK-5 is used as an alternative to conventional acid catalysts in the von Pechmann condensation of a neat mixture of substituted phenols with ethyl acetoacetate leading to the formation of coumarin derivatives at 130 °C. In comparison, CMK-5-SO3H showed a greater activity than some other homogeneous and heterogeneous catalysts. Additionally, the catalyst is reused repeatedly for 6 reaction cycles without any evidence of loss of activity, confirming the stability of the covalent bonding of acidic centers. The methodology presented offers reusable strategy for the efficient synthesis of coumarin, simplicity in operation, and green aspects by avoiding toxic conventional catalysts and solvents.
Zareyee, Daryoush,Serehneh, Mahshad
p. 88 - 91
(2014/05/20)

Diazabicyclo[2.2.2]octane stabilized on Fe3O4 as catalysts for synthesis of coumarin under solvent-free conditions
Fe3O4-diazabicyclo[2.2.2]octane (Fe3O 4-DABCO) magnetic nanoparticles (MNPs) catalyst was readily prepared from inexpensive starting materials in aqueous media which catalyzed the synthesis of coumarin. FTIR spectroscopy, X-ray diffraction, transmission electron micrographs were employed to characterize the properties of the synthesized Fe3O4-DABCO MNPs. High catalytic activity and ease of recovery from the reaction mixture using external magnet, and several reuse times without significant losses in performance are additional eco-friendly attributes of this catalytic system.
Nasseri, Mohammad Ali,Sadeghzadeh, Seyed Mohsen
p. 27 - 33
(2014/01/23)

CuFe2O4 nanoparticles: A magnetically recoverable and reusable catalyst for the synthesis of coumarins via pechmann reaction in water
The synthesis of coumarins by hydroxyalkylation of phenols with ethyl acetoacetate (via Pechmann reaction) is attempted using magnetically separable and reusable CuFe2O4 nanoparticles in water. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.] Copyright
Baghbanian, Seyed Meysam,Farhang, Maryam
p. 697 - 706
(2014/01/17)

Cholinium ionic liquids as cheap and reusable catalysts for the synthesis of coumarins via Pechmann reaction under solvent-free conditions
A cheap cholinium ionic liquid N,N′-dimethylaminoethanol hydrosulfate ([N112OH][HSO4]) was found to be an efficient and reusable catalyst for the Pechmann condensation under solvent-free conditions. The coumarin products can be simply separated and the ionic liquid catalyst can be recycled and reused for at least six runs without noticeable decrease in the catalytic activity. The UV-vis studies suggested that the increase of the acidity and the introduction of a hydroxyl group to the cation benefit the existence of the keto tautomer of ethyl acetoacetate, which then leads to the excellent performance of [N112OH][HSO4].
Zhang, Yuehua,Zhu, Anlian,Li, Qianqian,Li, Lingjun,Zhao, Yang,Wang, Jianji
p. 22946 - 22950
(2014/06/24)

Identification and characterization of novel inhibitors of mammalian aspartyl aminopeptidase
Aspartyl aminopeptidase (DNPEP) has been implicated in the control of angiotensin signaling and endosome trafficking, but its precise biologic roles remain incompletely defined. We performed a high-throughput screen of ～25,000 small molecules to identify inhibitors of DNPEP for use as tools to study its biologic functions. Twenty-three confirmed hits inhibited DNPEP-catalyzed hydrolysis of angiotensin II with micromolar potency. A counter screen against glutamyl aminopeptidase (ENPEP), an enzyme with substrate specificity similar to that of DNPEP, identified eight DNPEP-selective inhibitors. Structure-activity relationships and modeling studies revealed structural features common to the identified inhibitors, including a metal-chelating group and a charged or polar moiety that could interact with portions of the enzyme active site. The compounds identified in this study should be valuable tools for elucidating DNPEP physiology. Copyright
Chen, Yuanyuan,Tang, Hong,Seibel, William,Papoian, Ruben,Oh, Ki,Li, Xiaoyu,Zhang, Jianye,Golczak, Marcin,Palczewski, Krzysztof,Kiser, Philip D.
p. 231 - 242
(2014/10/15)

Coumarin-containing photo-responsive nanocomposites for NIR light-triggered controlled drug release via a two-photon process
A new multifunctional nanovehicle for tumor therapy and cell imaging was fabricated by coating NIR light-responsive polymers (HAMAFA-b-DDACMM) onto the surface of octadecyltrimethoxysilane (C18)-modified hollow mesoporous silica nanoparticles (HMS@C18) via self-assembly. First, the targeting NIR light-responsive block copolymer was synthesized by the RAFT living polymerization of [7-(didodecylamino) coumarin-4-yl] methyl methacrylate with hydroxyethylacrylate and N-(3-aminopropyl) methacrylamide hydrochloride and then grafted with folic acid (FA). The copolymers could be disrupted by excitation by a femtosecond NIR light laser (800 nm) via a two-photon absorption process due to the high two-photon absorption cross-section of the coumarin moiety. In order to enhance the drug loading capacity and biological stability of the nanovehicle, HMS nanoparticles modified by hydrophobic octadecyl chains were selected as the "core", which had a considerable drug loading efficiency of more than 70%. Then the core-shell nanocomposites (HMS@C18@HAMAFA-b-DDACMM) were obtained by coating the amphiphilic copolymers onto the core via self-assembly. Under excitation by NIR light at 800 nm, the pre-loaded drugs could be released from the nanocomposites due to the degradation of the light-responsive copolymers and the release efficiency was correlated with the irradiation time and light power. The in vitro experiments indicated that the nanocomposites were easily targeted into the tumor cells that over-expressed folic acid receptor (FR(+)) such as KB cells by endocytosis. Furthermore, the copolymer itself had strong fluorescence, which could be used to track the process of drug delivery.
Ji, Weidong,Li, Najun,Chen, Dongyun,Qi, Xiuxiu,Sha, Wenwei,Jiao, Yang,Xu, Qingfeng,Lu, Jianmei
supporting information
p. 5942 - 5949
(2013/11/19)