A series of reductively activated 3,6 substituted 2,5-bis(aziridinyl)benzoquinones, designed as potential anti-tumour agents, was shown to interact with
DNA. This was assayed by studying the colony forming ability of
DNA-repair deficient E. coli K12 and the inactivation of bacteriophage M13mp19. The activities of the compounds as measured in the two assays show a good correlation. Reduction of the
quinone compounds is essential for activity in the two assays. Reduction activates opening of the
aziridine ring and formation of an alkylating species. The results suggest that steric factors are important in
DNA adduct formation. Methylation of the
aziridine rings decreases the activity. Bulky 3,6-substitutes also decrease the activity. No correlation is found between above-mentioned assays for
DNA modification and in vivo activity towards tumour cells. It is possible that, as well as
DNA, other cellular targets are involved. A correlation is observed between the
DNA modifying activity and toxicity against L1210 cells in vitro. The relative high activity against L1210 cells of
bromine substituted compounds is possibly related to alternative mechanisms in which
bromine acts as an efficient leaving group.