The antineoplastic behaviour of nitrosoureas: an ab initio study

Abstract

The present study is an attempt towards answering the basic question, ‘What contributes to the antineoplastic behaviour of nitrosoureas?’ In other words, ‘What is the active species generated in vivo which is responsible for the alkylation of DNA nucleic acid bases and what is the site of alkylation?’ Ab initio MO calculations have been performed on possible active species generated in vivo and their interactions with guanine and cytosine have been studied in detail. The results indicate that the generation of the vinyl carbocation and its complexation with guanine and cytosine is responsible for the antineoplastic behaviour of the nitrosoureas. Detailed intermolecular interaction calculations have also been performed to study some recently proposed mechanisms for sequence specific reactions where the alkylation takes place before the dissociation of nitrosourea.