Comparative physico-chemical properties, biological effects, and disposition in mice of four nitrogen mustards

Abstract

Chlorambucil, phenyl acetic mustard, melphalan and mitoclomine are aromatic nitrogen mustard derivatives. These drugs show a fairly wide range of chemical reactivity and lipophilicity. In the series presently investigated, the more hydrophilic compounds (melphalan and phenyl acetic mustard) are the more toxic to mice and also the more active against Moloney sarcoma implanted IP in mice. No clear relation could be shown between the alkylating activity and the biological efficiency. All the compounds induce changes in DNA synthesis with differences between the timing of alterations and recovery. Nevertheless, return to pretreatment levels of thymidine incorporation is more rapid in the bone marrow and intestinal mucosa following administration of the drugs, than in tumor cells. The 14C-ethyl labeled compounds was used to investigate the part of the carrying structure in their disposition in mice.