13176-46-0Relevant articles and documents
Chromophore-linked substrate (CLS405): Probing metallo-β-lactamase activity and inhibition
Makena, Anne,Van Berkel, Sander S.,Lejeune, Clarisse,Owens, Raymond J.,Verma, Anil,Salimraj, Ramya,Spencer, James,Brem, Juergen,Schofield, Christopher J.
, p. 1923 - 1929 (2013)
Serine- and metallo-β-lactamases present a threat to the clinical use of nearly all β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. Efforts to develop metallo-β-lactamase (MBL) inhibitors require suitable screening platforms to allow the rapid determination of β-lactamase activity and efficient inhibition. Unfortunately, the platforms currently available are not ideal for this purpose. Further progress in MBL inhibitor identification requires inexpensive and widely applicable assays. Herein the identification of an inexpensive and stable chromogenic substrate suitable for use in assays of clinically relevant MBLs is described. (6R,7R)-3-((4-Nitrophenoxy)methyl)-8-oxo-7-(2-phenylacetamido) -5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 5,5-dioxide (CLS405) was synthesised in a three-step protocol. CLS405 was then characterised spectroscopically, and its stability and kinetic properties evaluated. With a Δλmax value of 100 nm between the parent and hydrolysis product, a higher analytical accuracy is possible with CLS405 than with commonly used chromogenic substrates. The use of CLS405 in assays was validated by MBL activity measurements and inhibitor screening that resulted in the identification of N-hydroxythiazoles as new inhibitor scaffolds for MBLs. Further evaluation of the identified N-hydroxythiazoles against a panel of clinically relevant MBLs showed that they possess inhibitory activities in the mid- to low-micromolar range. The findings of this study provide both a useful tool compound for further inhibitor identification, and novel scaffolds for the design of improved MBL inhibitors with potential as antibiotics against resistant strains of bacteria. Monitoring MBLs! Resistance to β-lactam antibiotics, mediated by metallo-β-lactamases (MBLs), is an increasing clinical problem. While compounds that target MBLs could be useful antibacterial agents, their identification is hampered by the lack of suitable assay platforms. To this end, CLS405, a chromophore-linked MBL substrate, was developed and its applicability demonstrated by the identification of N-hydroxythiazoles as potential inhibitors against a panel of clinically relevant MBLs. Copyright
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Kharasch,Sternfeld,Mayo
, p. 1655 (1937)
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Fluorescence ratiometric zinc sensors based on controlled energy transfer
Woo, Hana,You, Youngmin,Kim, Taehee,Jhon, Gil-Ja,Nam, Wonwoo
, p. 17100 - 17112 (2012)
The high-fidelity detection of labile zinc is of central importance for understanding the molecular mechanisms that link zinc homeostasis and human pathophysiology. Fluorescence ratiometric sensors are most suitable for the detection and trafficking of intracellular zinc ions. Here, we report the development of fluorescence ratiometric zinc sensors (HN1 and HN2) based on two-fluorophore platforms. The sensor constructs include blue fluorescent umbelliferone and an energy-accepting chromophore that absorbs the blue fluorescence. Zinc binding was found to promote fluorescence turn-on of the umbelliferone emission by suppression of intramolecular photoinduced electron transfer, thereby facilitating resonance energy transfer to the energy acceptors. The net observables were the fluorescence ratiometric changes, the extent of which depended strongly on the chemical structures of the acceptors. Photophysical investigations, including steady-state and transient photoluminescence spectroscopy, suggested a mechanism for the fluorescent zinc response that involved a combination of the intramolecular electron transfer and the interchromophoric energy transfer. The zinc probes displayed sensing capability that is suitable for the detection of biological zinc ions, with good selectivity, pH tolerance, and appropriate Kd values. Finally, zinc detection was demonstrated by fluorescence ratiometric visualization of exogenously supplied zinc ions in live HeLa cells. The probes enabled the reliable monitoring of zinc equilibration across the cell membrane. The Royal Society of Chemistry 2012.
Facile synthesis of β-ketoesters mediated by Sml2: Reformatsky reaction type selfcondensation
Park, Heui Sul,Lee, In Sang,Kim, Yong Hae
, p. 1673 - 1674 (1995)
α-Bromoesters are converted to β-ketoesters by treatment with samarium diiodide via self condensation under the mild conditions. The reaction appears to be initiated via the formation of samariun diiodide ester enolate for the Reformatsky reation type.
Target-Directed Azide-Alkyne Cycloaddition for Assembling HIV-1 TAR RNA Binding Ligands
Dash, Jyotirmayee,Dutta, Debasish,Paul, Raj,Paul, Rakesh
, p. 12407 - 12411 (2020)
The highly conserved HIV-1 transactivation response element (TAR) binds to the trans-activator protein Tat and facilitates viral replication in its latent state. The inhibition of Tat–TAR interactions by selectively targeting TAR RNA has been used as a strategy to develop potent antiviral agents. Therefore, HIV-1 TAR RNA represents a paradigmatic system for therapeutic intervention. Herein, we have employed biotin-tagged TAR RNA to assemble its own ligands from a pool of reactive azide and alkyne building blocks. To identify the binding sites and selectivity of the ligands, the in situ cycloaddition has been further performed using control nucleotide (TAR DNA and TAR RNA without bulge) templates. The hit triazole-linked thiazole peptidomimetic products have been isolated from the biotin-tagged target templates using streptavidin beads. The major triazole lead generated by the TAR RNA presumably binds in the bulge region, shows specificity for TAR RNA over TAR DNA, and inhibits Tat–TAR interactions.
A Novel Minor Groove Binder as a Potential Therapeutic Agent for Myotonic Dystrophy Type 1
Li, Ke,Krueger, Sarah B.,Zimmerman, Steven C.
, p. 2638 - 2644 (2021)
Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disorder that is inherited in an autosomal dominant manner. DM1 originates in a (CTG?CAG) repeat expansion in the 3’-UTR of the dystrophia myotonic protein kinase (DMPK) gene on chromosome 19. One of the transcripts, r(CUG)exp, is toxic in various ways. Herein we report a rationally designed small molecule with a thiazole peptidomimetic unit that can serve as a minor groove binder for the nucleic acid targets. This peptide unit linked to two triaminotriazine recognition units selectively binds to d(CTG)exp to inhibit the transcription process, and also targets r(CUG)exp selectively to improve representative DM1 pathological molecular features, including foci formation and pre-mRNA splicing defects in DM1 model cells. As such, it represents a new structure type that might serve as a lead compound for future structure-activity optimization.
Imidazo[1,2-a]pyridin-2-ylacetic acid and two pairs of isomorphous ML 2(H2O)2 dihydrates (M = Ni, Co and Mn, Cd) based on its anion: Syntheses, crystal structures and properties
Dylong, Agnieszka,Sowa, Micha?,Goldeman, Waldemar,?lepokura, Katarzyna,Duczmal, Marek,Wojciechowska, Agnieszka,Matczak-Jon, Ewa
, p. 9 - 21 (2014)
Imidazo[1,2-a]pyridin-2-ylacetic acid (HL, 1) and four ML 2(H2O)2·2H2O (M = Ni (2), Co (3), Mn (4), Cd (5)) complexes formed by its anion were synthesized, structurally characterized by single-crystal X-ray diffraction and investigated in terms of their thermal stability. In addition, magnetic properties of 2-4 are reported and the NIR-Vis-UV spectra of 2 and 3 are discussed in details. The crystal of 1 comprises 2D hydrogen bonded networks held in the crystal lattice by weak C-H.
Phosphine-Mediated Iterative Arene Homologation Using Allenes
Zhang, Kui,Cai, Lingchao,Jiang, Xing,Garcia-Garibay, Miguel A.,Kwon, Ohyun
, p. 11258 - 11261 (2015)
A PPh3-mediated multicomponent reaction between o-phthalaldehydes, nucleophiles, and monosubstituted allenes furnishes functionalized non-C2-symmetric naphthalenes in synthetically useful yields. When the o-phthalaldehydes were reacted with 1,3-disubstituted allenes in the presence of PPh2Et, naphthalene derivatives were also obtained in up to quantitative yields. The mechanism of the latter transformation is straightforward: aldol addition followed by Wittig olefination and dehydration. The mechanism of the former is a tandem γ-umpolung/aldol/Wittig/dehydration process, as established by preparation of putative reaction intermediates and mass spectrometric analysis. This transformation can be applied iteratively to prepare anthracenes and tetracenes using carboxylic acids as pronucleophiles.
Design, synthesis, molecular docking, anti-proliferative and anti-TB studies of 2H-chromen-8-azaspiro[4.5]decane-7,9-dione conjugates
Mane, Smita G.,Reddy, Dinesh S.,Katagi, Kariyappa S.,Kumar, Amit,Munnolli, Ravindra S.,Kadam, Nikhil S.,Akki, Mahesh C.,Nagarajaiah,Joshi, Shrinivas D.
, (2021)
In this work, a series of new 8-[(substituted 2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione derivatives (1a - 1l) is synthesized and characterized by 1H NMR, 13C NMR, FT-IR, GC-MS and elemental analysis. In addition, the structure of compound 1k has been elucidated using single crystal X-ray diffraction techniques. The synthesized compounds are screened for their anticancer and anti-TB activity. Preliminary anticancer results showed that compounds (1a- 1l) exhibit moderate to potent activity against MDA-MB-231, A549, HT-29 and Hela cancer cell lines. Compound 1f exhibited the most potent activity against MDA-MB-231cell line with IC50 value of 9.05 μM concentration, compound 1g and 1h showed potent activity against A549 cell line with IC50 value of 7.05 and 13.31 μM concentration respectively. Compound 1j showed good cytotoxicity against Hela cell line with IC50 of 16.14 μM, whereas, compound 1l is found to be moderately active against HT-29 cell line with IC50 of 18.07 μM. Anti-tubercular activity revealed that compound 1c, 1d, 1g, 1h and 1j have significant activity against MTBH37Rv strain with MIC 0.78, 1.56, 0.19, 0.39 and 0.78 μg/mL respectively. Further, to investigate the mechanism of anti-TB activity and detailed intermolecular interactions between the synthesized compounds, molecular docking studies are performed.
Microwave facilitated one-pot three component synthesis of coumarin-benzoxazole clubbed 1,2,3-triazoles: Antimicrobial evaluation, molecular docking and in silico ADME studies
Nesaragi, Aravind R.,Kamble, Ravindra R.,Bayannavar, Praveen K.,Metre, Tukaram V.,Kariduraganavar, Mahadevappa Y.,Margankop, Sheetal B.,Joshi, Shrinivas D.,Kumbar, Vijay M.
, p. 3460 - 3472 (2021/10/02)
4-((4-((Benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-2H-chromen-2-ones 7k–z were synthesized by conventional as well as microwave irradiation method in order to obtain antimicrobial agents. The present green synthetic protocol explores facile work up procedure with excellent yields (82–92%) and purity. Docking studies exhibited strong binding interactions with enzyme N-myristoyl transferase (PDB ID: 4CAW) with excellent C-score values. Compounds 7k–z were screened for their in vitro antimicrobial activities. The compounds 7w and 7 y exhibited excellent antimicrobial results for all the tested microorganisms at MICs ranging from 3.12 to 6.25 μg/ml in comparison with the marketed drugs.
