Search results for " oxadiazole"

Curcumin-like compounds designed to modify amyloid beta peptide aggregation patterns

2017

International audience; Curcumin is a natural polyphenol able to bind the amyloid beta peptide, which is related to Alzheimer's disease, and modify its self-assembly pathway. This paper focuses on a multi-disciplinary study that starts from the design of curcumin-like compounds with the key chemical features required for inhibiting amyloid beta aggregation, and reports the effects of these compounds on the in vitro aggregation of amyloid beta peptides. Chemoinformatic screening was performed through the calculation of molecular descriptors that were able to highlight the drug-like profile, followed by docking studies with an amyloid beta peptide fibril. The computational design underlined t…

Investigation on Quantitative Structure-Activity Relationships of 1,3,4-Oxadiazole Derivatives as Potential Telomerase Inhibitors.

2020

Background:Telomerase, a reverse transcriptase, maintains telomere and chromosomes integrity of dividing cells, while it is inactivated in most somatic cells. In tumor cells, telomerase is highly activated, and works in order to maintain the length of telomeres causing immortality, hence it could be considered as a potential marker to tumorigenesis.A series of 1,3,4-oxadiazole derivatives showed significant broad-spectrum anticancer activity against different cell lines, and demonstrated telomerase inhibition.Methods:This series of 24 N-benzylidene-2-((5-(pyridine-4-yl)-1,3,4-oxadiazol-2yl)thio)acetohydrazide derivatives as telomerase inhibitors has been considered to carry out QSAR studies…

Asymmetric synthesis and biological evaluation of 1,2,4-Oxadiazoles analogues of Linezolid

2014

Oxazolidinones are a class of antibacterial agents which displayed activity againist a variety of gram-positive pathogens and are highly potent against multidrug-resistant bacteria. Linezolid is the first oxazolidinone antibiotic approved for clinical use but linezolid resistance began to appear. 1,2,4 – Oxadiazoles are known bioactive heterocycles whose activity has been often associated to their bioisosterism with amide or ester functionalities [1]. As results of a research project on the molecular design of heterocycle – based antibacterials to contrast Multi-Drug Resistance (MDR) [2], we report the synthesis of 1,2,4 - Oxadiazole analogues of Linezolid. The synthesis has been achieved b…

Identification and validation of novel molecules obtained by integrated computational and experimental approaches for the read-through of PTCs in CF …

2015

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, 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…

The new era of 1,2,4-oxadiazoles

2009

The synthesis, the chemical and photochemical reactivity, and the use of 1,2,4-oxadiazoles in materials and as bioactive compounds have been reviewed. The material in this survey includes some historical background, general features, state-of-the-art applications together with a critical discussion about current limitations and suggestions for future developments.