Cytotoxic Agents Designed To Be Selective for Liver Cancer2

Abstract

A series of azobenzene compounds was prepared containing an alkylating group chemically unreactive because of the deactivating influence of the azo linkage. Members of the series containing a carboxyl group ortho to the azo linkage were readily reduced by rat-liver azo reductase. In some compounds the metabolite formed on reduction was highly cytotoxic but only had a short half life (41 seconds). Such chemicals might be useful in the treatment of liver cancer. The administered alkylating agent was unreactive and nontoxic but was converted in the liver to a toxic metabolite. Because of the rapid hydrolysis of the metabolite, the effects of such compounds may be largely confined to the liver and be less damaging to bone marrow than conventional alkylating agents.