Search results for "thiophenes"
showing 10 items of 80 documents
Efficient synthesis and 5-LOX/COX-inhibitory activity of some 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives
2012
Abstract A series of 3-hydroxybenzo[ b ]thiophene-2-carboxylic acid derivatives has been prepared and subsequently evaluated with regards to the inhibition of 5-LOX/COX. Structure optimization furnished derivatives with promising in vitro activity as dual 5-LOX/COX inhibitors with submicromolar IC 50 values for inhibition of 5-LOX and COX-1, respectively.
Antibodies directed to drug epitopes to investigate the structure of drug-protein photoadducts. Recognition of a common photobound substructure in ti…
2001
Drug-induced photoallergy is an immune adverse reaction to the combined effect of drugs and light. From the mechanistic point of view, it first involves covalent binding of drug to protein resulting in the formation of a photoantigen. Hence, determination of the structures of drug-protein photoadducts is of great relevance to understand the molecular basis of photoallergy and cross-immunoreactivity among drugs. Looking for new strategies to investigate the covalent photobinding of drugs to proteins, we generated highly specific antibodies to drug chemical substructures. The availability of such antibodies has allowed us to discriminate between the different modes by which tiaprofenic acid (…
Trichinella spiralisThymidylate Synthase: Developmental Pattern, Isolation, Molecular Properties, and Inhibition by Substrate and Cofactor Analogues
1996
Abstract Thymidylate synthase specific activity was found to remain at a constant level in crude extracts from muscle larvae, isolated (1-15 months after infection) by pepsin-HCl digestion, as well as from adult worms ofTrichinella spiralis.The enzyme was purified and its molecular (monomer mol. wt 35 kD) and kinetic (sequential mechanism with the Kmvalues 3.1 and 19 μM for dUMP and N5,10-methylenetetrahydrofolate, respectively) properties determined. 5-Fluoro-dUMP was a competitive, slow-binding inhibitor of the parasite enzyme. N5,10-methylenetetrahydrofolate analogues 10-propargyl-5,8-dideazafolate (CB3717), ZD1694, BW1843U89, and AG337 were weaker inhibitors of the parasite than regener…
Discovery and validation of small-molecule heat-shock protein 90 inhibitors through multimodality molecular imaging in living subjects.
2012
Up-regulation of the folding machinery of the heat-shock protein 90 (Hsp90) chaperone protein is crucial for cancer progression. The two Hsp90 isoforms (α and β) play different roles in response to chemotherapy. To identify isoform-selective inhibitors of Hsp90(α/β)/cochaperone p23 interactions, we developed a dual-luciferase (Renilla and Firefly) reporter system for high-throughput screening (HTS) and monitoring the efficacy of Hsp90 inhibitors in cell culture and live mice. HTS of a 30,176 small-molecule chemical library in cell culture identified a compound, N -(5-methylisoxazol-3-yl)-2-[4-(thiophen-2-yl)-6-(trifluoromethyl)pyrimidin-2-ylthio]acetamide (CP9), that binds to Hsp90(α/β) an…
Predicting 19F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex
2020
Abstract The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable 19F chemical‐shift predictions to deduce ligand‐binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the 19F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleepi…
Synthesis and biological evaluation of 2-(3 ',4 ',5 '-trimethoxybenzoyl)-3-amino 5-aryl thiophenes as a new class of tubulin inhibitors
2006
2-(3',4',5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SARs were elucidated with various substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at the para-position of the 5-phenyl group showed antiproliferative activity in the order of F=CH(3) > OCH(3)=Br=NO(2) > CF(3)=I > OEt. Several of these compounds led to arrest of HL-60 cells in the G2/M phase of the cell cycle and induction of apoptosis.
Identification and optimization of small molecule antagonists of vasoactive intestinal peptide receptor-1 (VIPR1).
2012
Identification, synthesis and structure-activity relationship of small-molecule VIPR1 antagonists encompassing two chemical series are described.
NLO properties of polythiophenes galvanostatically electrodeposited on ITO glasses
2008
International audience; A study of nonlinear optical properties of ClO4-doped polythiophenes, galvanostatically electrodeposited on ITO glasses, was carried out using second and third harmonic generation measurements. The effect of the oxidation state of the polymeric films was studied by comparing the nonlinear optical response of oxidised and reduced polythiophenes. Reduced polymeric films show higher values of the second and third order susceptibilities and a lower absorbance in respect to the oxidised ones. The morphology of the polythiophene films was studied by scanning electron and atomic force microscopes.
Donor-Acceptor Polythiophene Copolymers with Tunable Acceptor content for Photoelectric Conversion Devices
2004
The synthesis and characterization of a new series of substituted polythiophenes containing an electron acceptor anthraquinone moiety in the side chain are reported. The acceptor molar content was varied by the co-polymerization of both alkylthiophene and thiophene bearing anthraquinone monomers in different ratios. NMR analysis shows a good correlation between the monomer feed composition at the beginning of the polymerization and the actual unit composition of the backbone. The conjugation length and the chemical composition of the copolymers as a function of the molecular weight have been studied by size exclusion chromatography. Small angle X-ray scattering and UV-Vis absorption spectra…
Synthesis and photophysical properties of hyperbranhced polyfluorenes containing 2,4,6-tris(tiophen-2-yl)-1,3,5-triazine as the core
2011
A series of new hyperbranched polymers containing a 2,4,6-tris(thiophen-2-yl)-1,3,5-triazine core unit and polyfluorene chain arms have been synthesized via Suzuki coupling, and characterized by NMR, IR and GPC. All the polymers exhibit good thermal stability with a high decomposition temperature. By changing the 2,4,6-tris(thiophen-2-yl)-1,3,5-triazine/fluorene ratio the UV-vis absorption and emission spectra can be partially tuned. It has been found that the polymers containing a low ratio of 2,4,6-tris(thiophen-2-yl)-1,3,5-triazine units (P1-P3) have an absorption maximum around 385 nm, localized in the polyfluorene chain, and a shoulder around 425 nm ascribable to a charge transfer stat…