Trimethoprim Stimulates T-Cells through Metabolism-Dependent and -Independent Pathways
MRC Centre for Drug Safety Science, Department of Pharmacology, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, L69 3GE, England.Chemical Research in Toxicology (Impact Factor: 3.53). 06/2011; 24(6):791-3. DOI: 10.1021/tx2001256
Pathways of drug-specific T-cell stimulation have not been fully defined. The aim of this study was to use T-cell clones from a patient hypersensitive to the drug trimethoprim to characterize the involvement of drug metabolism and processing in antigen presentation and cross-reactivity patterns. The MHC-restricted CD4+ and CD8+ T-cell response was dependent on the presence of antigen-presenting cells, and both processing-dependent and -independent pathways of antigen presentation were detected. Stimulation of certain clones was blocked through inhibition of drug-metabolizing enzyme activity. Trimethoprim clones were additionally stimulated with diaveridine and pyrimethamine but not other closely related structures.
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ABSTRACT: A new ligand bearing two tpy moieties and one bpy unit (tpy = 2,2':6',2''-terpyridine; bpy = 2,2'-bipyridine) linked by carbon-carbon single bonds and its corresponding trinuclear ruthenium complex were readily synthesized in high yield, and characterized by (1)H NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HR-ESI/MS) and elemental analysis. The ruthenium complex exhibited moderate catalytic activity towards selective oxidation of alcohols in water with visible light under an air atmosphere. Investigations of UV/vis spectra, electrochemistry and ESI/MS suggested that the catalytic cycle involves two processes, Ruc(II)-OH2/Ruc(III)-OH and Ruc(III)-OH/Ruc(IV)[double bond, length as m-dash]O. The effective electron transfer from the excited state *[Ru(tpy)2](2+) to [Co(NH3)5Cl]Cl2 is proposed to be responsible for the good activities of this visible-light-driven system under an air atmosphere.
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