Search results for "Pyrimidine"
showing 10 items of 589 documents
Conical nanopores highlight the pro-aggregating effects of pyrimethanil fungicide on Aβ(1-42) peptides and dimeric splitting phenomena.
2022
International audience; The Aβ(1-42) aggregation is a key event in the physiopathology of Alzheimer's disease (AD). Exogenous factors such as environmental pollutants, and more particularly pesticides, can corrupt Aβ(1-42) assembly and could influence the occurrence and pathophysiology of AD. However, pesticide involvement in the early stages of Aβ(1-42) aggregation is still unknown. Here, we employed conical track-etched nanopore in order to analyse the Aβ(1-42) fibril formation in the presence of pyrimethanil, a widely used fungicide belonging to the anilinopyrimidine class. Our results evidenced a pro-aggregating effect of pyrimethanil on Aβ(1-42). Aβ(1-42) assemblies were successfully d…
Specific detection of cyclobutane pyrimidine dimers in phytoplankton DNA by a non-radioactive assay based on T4-endonuclease V digestion.
2001
The effect of artificial and natural UV irradiation on DNA in marine phytoplankton Isochrysis galbana monoculture was investigated. The presence of cyclobutane pyrimidine dimers (CPDs) in unlabelled I. galbana DNA was detected by a non-radiometric alkaline filter elution assay after T4-endonuclease V digestion. The quantity of CPDs was estimated by alkaline agarose gel electrophoresis. Precise determination of the amount of DNA in the presence of I. galbana pigments was achieved by oxazole yellow homodimer (YOYO) dye. T4-endonuclease V-sensitive sites frequency (ESS/kb), measured after exposure to 2-40 kJ m(-2) of artificial UV light, increased in a dose-dependent manner. Twelve hours after…
Immunoreagent generation and competitive assay development for cyprodinil analysis.
2012
Cyprodinil is an anilinopyrimidine fungicide applied worldwide for the prevention and treatment of highly destructive plant diseases in a large variety of crops, including cereals, fruits, and vegetables. This paper describes the development of the first reported immunoassays for cyprodinil. Two original haptens have been synthesized and conjugated to different carrier proteins, and polyclonal antibodies have been produced. Moreover, competitive enzyme-linked immunosorbent assays have been developed and characterized for the analysis of this widely used pesticide. The influence of organic solvents and buffer conditions over the assay analytical parameters was studied. The IC 50 values of th…
The Co‐mutational Spectrum Determines the Therapeutic Response in Murine FGFR2 Fusion‐Driven Cholangiocarcinoma
2021
Background and aims Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and a highly lethal malignancy. Chemotherapeutic options are limited, but a considerable subset of patients harbors genetic lesions for which targeted agents exist. Fibroblast growth factor receptor 2 (FGFR2) fusions belong to the most frequent and therapeutically relevant alterations in ICC, and the first FGFR inhibitor was recently approved for the treatment of patients with progressed, fusion-positive ICC. Response rates of up to 35% indicate that FGFR-targeted therapies are beneficial in many but not all patients. Thus far, no established biomarkers exist that predict resistance or r…
Diuretika, 3. Mitt. 1-Carbocyclisch und heterocyclisch substituierte 4-Aminopyrazolo[3,4-d]pyrimidine
1981
In Anlehnung an das diuretisch wirksame 4,6-Diamino-1-(2-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin wurden durch Kondensation der 5-Amino-4-cyanpyrazole 1a–g mit Formamid (2) die korrespondierenden 4-Aminopyrazolo[3,4-d]pyrimidine 3a–g dargestellt. Diuretics, III: 4-Aminopyrazolo[3,4-d]pyrimidines with Carbocyclic or Heterocyclic Substituents at N-1 As analogues of the diuretically active 4,6-diamino-1-(2-pyridyl)-1H-pyrazolo[3,4-d]pyrimidine, the 4-aminopyrazolo[3,4-d]pyrimidines 3a–g were prepared by condensation of the 5-amino-4-cyanopyrazoles 1a–g with formamide (2).
Isomer-nonspecific action of dichlorodiphenyltrichloroethane on aryl hydrocarbon receptor and G-protein-coupled receptor 30 intracellular signaling i…
2014
Abstract Extended residual persistence of the pesticide dichlorodiphenyltrichloroethane (DDT) raises concerns about its long-term neurotoxic effects. Little is known, however, about DDT toxicity during the early stages of neural development. This study demonstrated that DDT-induced apoptosis of mouse embryonic neuronal cells is a caspase-9-, caspase-3-, and GSK-3β-dependent process, which involves p,p’ -DDT-specific impairment of classical ERs. It also provided evidence for DDT-isomer-nonspecific alterations of AhR- and GPR30-mediated intracellular signaling, including changes in the levels of the receptor and receptor-regulated mRNAs, and also changes in the protein levels of the receptors…
Fanconi's anaemia cells have normal steady-state levels and repair of oxidative DNA base modifications sensitive to Fpg protein
1998
Abstract Cells from Fanconi's anaemia (FA) patients are abnormally sensitive to oxygen. However, a distinct genetic defect in either the cellular defence against reactive oxygen species (ROS) or in their metabolic generation has not been identified to date. Recently, the gene for the human 8-hydroxyguanine (8-oxoG) glycosylase, which removes this oxidative base modification from the genome, has been localized on chromosome 3p25, i.e., in the same region as the FA complementation group D (FAD) gene. We therefore studied the removal of photosensitization-induced 8-oxoG residues from the DNA of FA cells, using Fpg protein, the bacterial 8-oxoG glycosylase, to quantify the lesions by alkaline e…
tert-Butoxyl radicals generate mainly 7,8-dihydro-8-oxoguanine in DNA.
2000
Abstract Like hydroxyl radicals, alkoxyl radicals have been implicated in the generation of cellular oxidative DNA damage under physiological conditions; however, their genotoxic potential has not yet been established. We have analyzed the DNA damage induced by a photochemical source of tert- butoxyl radicals, the water soluble peroxy ester [4-( tert -butyldioxycarbonyl)benzyl]triethylammonium chloride (BCBT), using various repair endonucleases as probes. The irradiation (UV 360 ) of BCBT in the presence of bacteriophage PM2 DNA was found to generate a DNA damage profile that consisted mostly of base modifications sensitive to the repair endonuclease Fpg protein. Approximately 90% of the mo…
Intra- and extra-cellular DNA damage by harmine and 9-methyl-harmine
2014
It is known that b-carbolines are able to produce photosensitized damage in cell-free DNA, but there is little information on their effects on cellular DNA. Therefore, we have analyzed the DNA damage produced by harmine and 9-methyl-harmine under UVA irradiation in V79 cells, together with the associated generation of micronuclei and photocytotoxicity. The results indicate that the most frequent photoproducts generated in the cellular DNA are modified purines such as 8-oxo-7,8-dihydroguanine. Only relatively few single-strand breaks were observed. CPDs were absent, although they were generated in cell-free DNA irradiated under the same conditions. The overall extent of DNA damage in the cel…
Arylpyridines, arylpyrimidines and related compounds as potential modulator agents of the VEGF, hTERT and c-Myc oncogenes.
2019
Twenty-four derivatives structurally related to honokiol have been synthesized and biologically evaluated. IC50 values were determined towards the HT-29, MCF-7 and HEK-293 cell lines. Some of these derivatives exhibited comparable or lower IC50 values than honokiol towards the HT-29 and MCF-7 cell lines or else higher selectivity indexes than the natural product. Twelve selected derivatives were evaluated for their ability to inhibit the expression of the VEGFA, hTERT and c-Myc genes and also to inhibit the production of total c-Myc protein and the secretion of the VEGF protein. One of the most promising compounds, 3-(2,4-dimethoxyphenyl)pyridine, may be a good candidate for further studies…