Rhj. Hargreaves et al., Cross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents, J MED CHEM, 42(12), 1999, pp. 2245-2250
The cytotoxicities and DNA cross-linking abilities of several alkyl-substit
uted diaziridinylquinones have been investigated. The cytotoxicities were d
etermined in DT-diaphorase-rich (H460 and HT29) and -deficient (H596 and BE
) cell lines. It was shown that the cytotoxicities in these cell Lines corr
elated with the relative rates of reduction by the purified human enzyme an
d with the cross-linking efficiencies. The rates of reduction by DT-diaphor
ase were more dependent on the structures of the compounds than the reducti
on potentials, as determined by cyclic voltammetry. A computer model was al
so used to explain high efficiency of cross-linking and the GNC sequence se
lectivity of the reduced methyl-substituted diaziridinylquinones.