The Fate of 4-Cyanoacetanilide in Rats and Mice: The Mechanism of Formation of a Novel Electrophilic Metabolite
4-Cyanoacetanilide (PCAA, b in Scheme 1) is a metabolite of 4-cyano-N,N-dimethyl-aniline (CDA, Scheme 1). Whilst the metabolism of CDA, a designed analogue of butter yellow (Ashby, Styles, Paton, 1980) was being investigated, a novel involvement of glutathione was detected (Hutson, Lakeman and Logan, 1984). From the structure of the mercapturic acid conjugate (C), which was isolated from the urine of the rats that had been dosed with CDA, it was postulated that the CDA had been de-methylated (A), acetylated (b), and that the methyl group of the acetyl group had been activated to form an electrophilic intermediate, the intermediate then being trapped, at least in part, by glutathione and eventually excreted as the mercapturic acid (C). interestingly, mice seemed to be unable to form this electrophilic intermediate.
KeywordsMercapturic Acid Fast Atom Bombardment Mass Spectrometry Resultant Alcohol Amide Side Chain Magnetic Resonance Spectro
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- S. Edwards, D. Hesk, C. J. Logan, and R. Waters, 1985, in: 2nd U. K. Environmental Mutagen Society Ring-Test, eds. C. Arlot, J. Ashby, and J. Parry. Pub. McMillan, London.Google Scholar