131918-97-3Relevant articles and documents
Synthesis of isothiocyanate-derived mercapturic acids
Vermeulen, Martijn,Zwanenburg, Binne,Chittenden, Gordon J.F.,Verhagen, Hans
, p. 729 - 737 (2003)
Twelve mercapturic acids derived from saturated and unsaturated aliphatic and aromatic isothiocyanates were synthesised, by adding isothiocyanate to a solution of N-acetyl-L-cysteine and sodium bicarbonate, in a typical yield of 77%. Isothiocyanates were synthesised first by adding the corresponding alkyl bromide to phthalimide potassium salt. The obtained N-alkyl-phthalimide was hydrazinolysed yielding the alkyl amine, which subsequently was reacted with thiophosgene yielding the isothiocyanate with an overall yield of 16%. Mercapturic acids in urine can serve as a biomarker of intake to determine the health promoting potential of isothiocyanates present in cruciferous vegetables.
Inhibition of human leukaemia 60 cell growth by mercapturic acid metabolites of phenylethyl isothiocyanate
Adesida,Edwards,Thornalley
, p. 385 - 392 (2007/10/03)
Mercapturic acid pathway metabolites of phenylethyl isothiocyanate inhibited the growth of human leukaemia 60 (HL60) cells in vitro. The adduct with L-cysteine, S-(N-phenylethylthiocarbamoyl)cysteine, was the most potent with strong antileukaemic activity: the median growth inhibitory concentration (GC50) value was 336 ± 1 nM (N = 18) compared with GC50 values of the precursor formed from dietary glucosinolates, phenylethyl isothiocyanate, 1.49 ± 0.01 μM (N = 8), and the initial mercapturic acid pathway metabolite S-(N-phenylethylthiocarbamoyl)glutathione 5.46 ± 0.36 μM (N = 18). S-(N-Benzylthiocarbamoyl)cysteine and S-(N-phenylpropylthiocarbamoyl)cysteine also had antiproliferative activity but S-(N-phenylethylthiocarbamoyl)cysteine was the most potent compound studied. The latter induced DNA fragmentation in HL60 cells but DNA laddering characteristic of apoptosis was not observed. It had low toxicity to corresponding differentiated cells, neutrophils, in culture, and therefore the cytotoxicity had selectivity for leukaemia cells. The antiproliferative activity of S-(N-phenylethylthiocarbamoyl)cysteine was lost during preincubation with culture medium, attributed to S-thiocarbamoyl transfer to serum proteins, which may decrease its effectiveness in vivo. The antiproliferative activity of S-(N-phenylalkylthiocarbamoyl)cysteine derivatives, by inhibiting tumour growth in pre-clinical development, may contribute to the association of decreased cancer incidence with dietary glucosinolate consumption.