Cross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents

Citation
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
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry & Analysis
Journal title
JOURNAL OF MEDICINAL CHEMISTRY
ISSN journal
0022-2623 → ACNP
Volume
42
Issue
12
Year of publication
1999
Pages
2245 - 2250
Database
ISI
SICI code
0022-2623(19990617)42:12<2245:CASAOD>2.0.ZU;2-H
Abstract
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.