31655-50-2Relevant academic research and scientific papers
Synthesis of isothiocyanate-derived mercapturic acids
Vermeulen, Martijn,Zwanenburg, Binne,Chittenden, Gordon J.F.,Verhagen, Hans
, p. 729 - 737 (2007/10/03)
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.
Characterization of protein adducts produced by N-methyldithiocarbamate and N-methyldithiocarbamate esters
Valentine,Amarnath,Amarnath,Graham
, p. 254 - 261 (2007/10/03)
The toxicity of N-methyldithiocarbamate may be mediated through decomposition to more biologically active compounds. Two principal products, CS2 and methyl isothiocyanate, have the potential to interact covalently with macromolecules in biological systems. In this investigation the ability of N-methyldithiocarbamate to generate methyl isothiocyanate and CS2 under physiological conditions resulting in acylation and covalent cross-linking of proteins was examined using 13C NMR and GC/MS. Two N-methyldithiocarbamate esters, S-methyl N-methyldithiocarbamate and (N-acetyl-S- methylthiocarbamoyl)cysteine, were also investigated to evaluate the acylating ability of sulfhydryl conjugates of N-methyldithiocarbamate. The predominant and most stable adduct produced by the free dithiocarbamate and its S-substituted esters was methylthiourea on ε-lysyl and N-terminal α- amino groups. Derivatization on N-terminal amino groups progressed more rapidly for the dithiocarbamate than for its mercapturate. Methylurea protein adducts were also produced by the dithiocarbamate and its esters, suggesting production of methyl isocyanate in the decomposition of N- methyldithiocarbamate. Covalent cross-linking of β-lactoglobulin by N- methyldithiocarbamate resulting from its decomposition to CS2 was observed using denaturing polyacrylamide gel electrophoresis. These results demonstrate the ability of a monoalkyldithiocarbamate to acylate protein amino groups and effect covalent cross-linking. These processes represent molecular mechanisms that may contribute to the toxicity of this class of compounds.
