Search results for "Diazole"

Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives.

2015

Abstract Premature stop codons are the result of nonsense mutations occurring within the coding sequence of a gene. These mutations lead to the synthesis of a truncated protein and are responsible for several genetic diseases. A potential pharmacological approach to treat these diseases is to promote the translational readthrough of premature stop codons by small molecules aiming to restore the full-length protein. The compound PTC124 (Ataluren) was reported to promote the readthrough of the premature UGA stop codon, although its activity was questioned. The potential interaction of PTC124 with mutated mRNA was recently suggested by molecular dynamics (MD) studies highlighting the importanc…

Identification of a new molecule with readthrough activity to rescue CFTR protein function

In Cystic fibrosis (CF) disease nonsense mutations in the CFTR gene cause absence of the CFTR protein expression and a more severe form of the disease. About 10% of patient affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by translational readthrough inducing drugs such as Ataluren. In this context we aimed to compare the 1,2,4-oxadiazole core of Ataluren with a slightly different scaffold, the 1,3,4oxadiazole core. By a validated protocol consisting of computational screening, synthesis and biological tests we identified, a new small molecule with 1,3,4-oxadiazole core (2a/NV2445…

Transition Metal Complexes as DNA-intercalators

2008

Synthesis and characterization of a Cu(II) complex of 2-benzylmercapto-5- methyl-1,3,4-thiadiazole (C10H10N2S 2)

2008

A Cu(II) complex of 2-benzylmercapto-5-methyl-1,3,4-thiadiazole was synthesized and characterized. The crystal structure of the copper complex and the free ligand were determined by single-crystal X-ray diffraction at room temperature: {[Cu(C10H10N2S2) 2(Cl)2], P1 triclinic, a = 8.1450(2) Å, b = 8.1690(2) Å, c = 10.8180(3) Å, α = 97.4040(12)°, β = 101.6270(11)°, γ = 116.1431(14)°; C10H10N2S2 ligand, Pbca orthorhombic, a = 8.7938(7) Å, b = 9.6491(7) Å, c = 25.3552(18) Å}. The metal complex framework consists of discrete units that provide crystalline stability through a network of van der Waals contacts. The Cu(II) is coordinated by two chloride ions and two 2-benzylmercapto-5-methyl-1,3,4- …

CCDC 206077: Experimental Crystal Structure Determination

2006

Related Article: S.Azzouzi, M.El Messaoudi, M.Esseffar, R.Jalal, F.H.Cano, M.del Carmen Apreda-Rojas, L.R.Domingo|2005|J.Phys.Org.Chem.|18|522|doi:10.1002/poc.892

Toward a Rationale for the PTC124 (Ataluren) Promoted Readthrough of Premature Stop Codons: A Computational Approach and GFP-Reporter Cell-Based Assay

2014

The presence in the mRNA of premature stop codons (PTCs) results in protein truncation responsible for several inherited (genetic) diseases. A well-known example of these diseases is cystic fibrosis (CF), where approximately 10% (worldwide) of patients have nonsense mutations in the CF transmembrane regulator (CFTR) gene. PTC124 (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-benzoic acid), also known as Ataluren, is a small molecule that has been suggested to allow PTC readthrough even though its target has yet to be identified. In the lack of a general consensus about its mechanism of action, we experimentally tested the ability of PTC124 to promote the readthrough of premature termination c…

Hydrophobic pocket targeting probes for enteroviruses

2015

Visualization and tracking of viruses without compromising their functionality is crucial in order to understand virus targeting to cells and tissues, and to understand the subsequent subcellular steps leading to virus uncoating and replication. Enteroviruses are important human pathogens causing a vast number of acute infections, and are also suggested to contribute to the development of chronic diseases like type I diabetes. Here, we demonstrate a novel method to target site-specifically the hydrophobic pocket of enteroviruses. A probe, a derivative of Pleconaril, was developed and conjugated to various labels that enabled the visualization of enteroviruses under light and electron micros…

Synthesis, Reactivity, Biological Activity and Applications of Fluorinated Oxadiazoles and Thiadiazoles

2014

A literature survey of the chemistry of fluorinated oxadiazoles and thiadiazoles is presented. The core part on synthetic procedures is given by type of heterocycle and includes recent developments up to the end of 2012. Reactivity is discussed when induced by the presence of the fluorinated moiety. Selected examples of bioactive compounds and applications are illustrated.

An ANRORC approach to the synthesis of perfluoroalkylated 1,2,4-triazole-carboxamides

2009

A series of perfluoroalkyl-1,2,4-triazole-carboxamides has been obtained through an ANRORClike rearrangement (Addition of Nucleophile, Ring-Opening and Ring-Closure) of 5- perfluoroalkyl-1,2,4-oxadiazole-3-carboxamides with methylhydrazine or hydrazine. The initial addition of the bidentate nucleophile to the electrophilic C(5) of the 1,2,4-oxadiazole ring, followed by ring opening and ring closure, leads to the formation of triazoles in good yield under mild experimental conditions. In some cases, a competitive ANRORC-enlargement reaction to form 1,2,4-triazin-6-ones was also observed. Obtained carboxamidotriazoles have also been explored as precursors for the synthesis of 3(5)-perfluoroal…

Fluorescent Hg2+ Sensors: Synthesis and Evaluation of a Tren-Based Starburst Molecule Containing Fluorinated 1,2,4-Oxadiazoles.

2010

A new tren-based starburst molecule containing fluorinated 1,2,4-oxadiazoles as fluorophores has been synthesized and its sensing behavior toward several metal cations has been investigated by UV/Vis, fluorescence, 1 H NMR and 19 F NMR spectroscopy. Selective sensing for Hg 2+ ions through a PET-based mechanism was evidenced, suggesting application as fluorescent sensor for Hg 2+ of the off-on type.