THE ANTINEOPLASTIC BEHAVIOR OF NITROSOUREAS - AN AB-INITIO STUDY

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 r esponsible for the alkylation of DNA nucleic acid bases and what is th e site of alkylation?' Ab initio MO calculations have been performed o n possible active species generated in vivo and their interactions wit h guanine and cytosine have been studied in detail. The results indica te that the generation of the vinyl carbocation and its complexation w ith guanine and cytosine is responsible for the antineoplastic behavio ur of the nitrosoureas. Detailed intermolecular interaction calculatio ns have also been performed to study some recently proposed mechanisms for sequence specific reactions where the alkylation takes place befo re the dissociation of nitrosourea.