Synthesis and cytotoxic effects of hydroxymethyl-3-pyridyl- and 2-chloro-5-pyridyltriazene derivatives

3-Hydroxymethyl-3-methyl-1-(3-pyridyl)-triazene (III) and 3-hydroxymethyl-3-methyl-1-(2-chloro-5-pyridyl)-triazene (VI) were synthesized and their cytotoxic effects towards S180 cells compared with those of the corresponding dimethyltriazene and monomethyltriazene derivatives. The hydroxy-methyltriazenes were one to two orders of magnitude more inhibitory than the corresponding dimethyl analogs, as assessed by cell growth, colony forming and macromolecular synthesis assays. Comparable effects were observed with the related monomethyl triazenes indicating that the activity of (III) and (VI) could result, at least in part, from release of monomethyl derivatives. The corresponding dimethyltriazenes were much less toxic to S180 cells and exerted only an unspecific cytotoxic activity at the maximal attainable dose (5 X 10(-3) M). The cytotoxic activities of the tested triazenes were correlated with their chemical half-lives under near physiological conditions (pH 7.5).