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. 1987 Nov;84(21):7443–7447. doi: 10.1073/pnas.84.21.7443

Bioactivation mechanism of the cytotoxic and nephrotoxic S-conjugate S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine.

W Dekant 1, L H Lash 1, M W Anders 1
PMCID: PMC299312  PMID: 3478703

Abstract

The bioactivation of S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC) was studied with purified bovine kidney cysteine conjugate beta-lyase and with N-dodecylpyridoxal bromide in cetyltrimethylammonium bromide micelles as a pyridoxal model system. The beta-lyase and the pyridoxal model system converted CTFC to chlorofluoroacetic acid and inorganic fluoride, which were identified by 19F NMR spectrometry. 2-Chloro-1,1,2-trifluoroethanethiol and chlorofluorothionoacetyl fluoride were formed as metabolites of CTFC and were trapped with benzyl bromide and diethylamine, respectively, to yield benzyl 2-chloro-1,1,2-trifluoroethyl sulfide and N,N-diethyl chlorofluorothioacetamide, which were identified by gas chromatography/mass spectrometry. The bioactivation mechanism of CTFC therefore involves the initial formation of the unstable thiol 2-chloro-1,1,2-trifluoroethanethiol, which loses hydrogen fluoride to form the acylating agent chlorofluorothionoacetyl fluoride; hydrolysis of the thionoacyl fluoride affords the stable, terminal metabolites chlorofluoroacetic acid and inorganic fluoride. The intermediate acylating agent and chlorofluoroacetic acid may contribute to the cytotoxic effects of CTFC.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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