Triazene drug metabolites. Part 11. Synthesis of S-cysteinyl and related derivatives of N-hydroxymethyltriazenes

Abstract

S-Cysteinyl-, S-(N-acetyl)cysteinyl-, S-glutathionyl and some related thioether derivatives of anticancer triazenes have been synthesised in high yield. The synthesis involves reaction between N-alkyl-N-hydroxymethyltriazenes with cysteine, N-acetylcysteine, glutathione or appropriate thiol in trifluoroacetic acid. The cysteinyl derivative is not a substrate for a mammalian β-lyase. Consequently the cysteinyl, N-acetylcysteinyl and glutathionyl derivatives lack anticancer activity against the Walker, L1210 and V79 tumour cell lines, mutagenic activity against Salmonella TA 100 and TA 2638 cell lines and cytotoxicity against renal proximal tubule cells.