Identification of 4-(5-amino-2-furyl)thiazole (AFT) as a reductive metabolite of the carcinogen 4-(5-nitro-2-furyl)thiazole (NFT).
The chemical synthesis of 4-(5-amino-2-furyl)thiazole (AFT) and its formation during the in vitro reductive metabolism of 4-(5-nitro-2-furyl)thiazole (NFT) by rat liver tissues on anaerobic incubation with NADPH were examined. AFT was synthesized by catalytic reduction of NFT with 5% palladium on activated carbon. Purified AFT, a pale yellow powder, melted at 105 degrees C and had an extinction coefficient of 16.3 mM-1 cm-1 at 297 nm in methanol. The proton n.m.r. spectrum, i.r. and mass spectra were consistent with the assigned structure. Analysis of the ethyl acetate extract, following incubation of NFT with rat liver tissue preparations, revealed a metabolite whose chromatographic and mass spectral characteristics were the same as those obtained with synthetic AFT, thus establishing the structural identity of the metabolite as AFT. These data show that AFT is formed on reduction and could act as a precursor for the formation of 1-(4-thiazolyl)-3-cyano-1-propanone as postulated earlier.
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S
Swaminathan
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Ichikawa
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GT
Bryan
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005200:FANFT / Q000031:analogs & derivatives / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D051381:Rats; D013844:Thiazoles / Q000032:analysis* / Q000378:metabolism*
D013844:Thiazoles; D009249:NADP; C028999:4-(5-nitro-2-furyl)thiazole; D005200:FANFT; C048571:4-(5-amino-2-furyl)thiazole