Search results for "Pyrimidines"
showing 10 items of 167 documents
Review of the safety, tolerability, and drug interactions of the new antifungal agents caspofungin and voriconazole
2003
Managing invasive fungal infections often presents a challenge for clinicians in the treatment of immunocompromised patients. Two very different systemic antifungal agents, voriconazole and caspofungin, have recently been introduced into the market place. Voriconazole is a new triazole antifungal, while caspofungin is the first echinocandin antifungal. Voriconazole acts by inhibiting the synthesis of ergosterol in the fungal cell membrane. Caspofungin inhibits beta-1,3-D-glucan synthesis in the cell wall, a target present in fungal cells, but absent from mammalian cells. Both agents are broad-spectrum, with efficacy against invasive Aspergillus and Candida infections. The safety and tolerab…
In vitro activity of fluconazole, voriconazole and caspofungin against clinical yeast isolates.
2007
Predicting the clinical outcome of a systemic mycosis is often a difficult task, especially when microbiological resistance is one of the factors contributing to therapeutic failure. Some of these factors are host-related--e.g. immune state, site and severity of infection, poor compliance to therapy--while others are associated with the drug's characteristics--e.g. dosage, type of compound (fungistatic/fungicidal), pharmacokinetic properties and drug-drug interactions. In the last few years, clinicians have been confronted with the problem of selecting the most appropriate antifungal therapy for systemic infections and have highlighted the need for a reliable method to assay the in vitro su…
Intracellular retention of ABL kinase inhibitors determines commitment to apoptosis in CML cells
2012
PLoS one 7(7), e40853 (2012). doi:10.1371/journal.pone.0040853
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…
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…
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…
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…
Monoclonal antibody-based immunoassays for cyprodinil residue analysis in QuEChERS-based fruit extracts
2015
Cyprodinil is among the most common agrochemical residues found in highly perishable fruits, such as strawberries. In the present study, high-affinity monoclonal antibodies to this anilinopyrimidine fungicide were raised for the first time with the aim to produce valuable immunochemical analytical assays. Cyprodinil bioconjugates and the generated novel monoclonal antibodies were employed for sensitive competitive immunoassay development in two different formats. The limits of detection of the optimized assays were 20 and 30 ng L-1 for the indirect and direct assay, respectively. Influence over assay parameters of different physicochemical factors was studied. Strawberry samples were extrac…
Inhibition of Transfer to Secondary Receptors by Heparan Sulfate-Binding Drug or Antibody Induces Noninfectious Uptake of Human Papillomavirus
2007
ABSTRACT Infection with various human papillomaviruses (HPVs) induces cervical cancers. Cell surface heparan sulfates (HS) have been shown to serve as primary attachment receptors, and molecules with structural similarity to cell surface HS, like heparin, function as competitive inhibitors of HPV infection. Here we demonstrate that the N , N ′-bisheteryl derivative of dispirotripiperazine, DSTP27, efficiently blocks papillomavirus infection by binding to HS moieties, with 50% inhibitory doses of up to 0.4 μg/ml. In contrast to short-term inhibitory effects of heparin, pretreatment of cells with DSTP27 significantly reduced HPV infection for more than 30 h. Using DSTP27 and heparinase, we fu…