Cytotoxic sulphonamides designed for selective deposition in malignant tissue

Abstract

The tumour and liver concentrations of a range of sulphonamides of different pKa values have been measured. Although a number of them concentrated to a much greater extent in the mouse plasma cell tumour than in liver, no correlation was observed between this property and pKa value. A series of dimethyltriazenes were prepared from the sulphonamides and tested for their anti-tumour activity. Two dimethyltriazenes derived from sulphamerazine and sulphapyridine are highly selective anti-tumour agents but no evidence was obtained that this effect was due to their selective concentration in tumours. In tests against the TLX 5 lymphoma, a phenyltriazene was shown to be dose-schedule dependent, daily administration of the compound being more effective than single doses. The biological half-life of the phenyltriazenes was shown to be of importance in determining their anti-tumour effects, agents with longer half-lives being more active than agents of shorter half-lives.