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

J Med Chem. 1999 Jun 17;42(12):2245-50. doi: 10.1021/jm991007y.


The cytotoxicities and DNA cross-linking abilities of several alkyl-substituted diaziridinylquinones have been investigated. The cytotoxicities were determined in DT-diaphorase-rich (H460 and HT29) and -deficient (H596 and BE) cell lines. It was shown that the cytotoxicities in these cell lines correlated with the relative rates of reduction by the purified human enzyme and with the cross-linking efficiencies. The rates of reduction by DT-diaphorase were more dependent on the structures of the compounds than the reduction potentials, as determined by cyclic voltammetry. A computer model was also used to explain high efficiency of cross-linking and the GNC sequence selectivity of the reduced methyl-substituted diaziridinylquinones.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents, Alkylating / chemical synthesis*
  • Antineoplastic Agents, Alkylating / chemistry
  • Antineoplastic Agents, Alkylating / pharmacology
  • Aziridines / chemical synthesis*
  • Aziridines / chemistry
  • Aziridines / pharmacology
  • Cell Line
  • Cross-Linking Reagents / chemical synthesis*
  • Cross-Linking Reagents / chemistry
  • Cross-Linking Reagents / pharmacology
  • DNA / chemistry
  • DNA / metabolism*
  • Humans
  • Models, Molecular
  • NAD(P)H Dehydrogenase (Quinone) / deficiency
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Quinones / chemical synthesis*
  • Quinones / chemistry
  • Quinones / pharmacology


  • Antineoplastic Agents, Alkylating
  • Aziridines
  • Cross-Linking Reagents
  • Quinones
  • DNA
  • NAD(P)H Dehydrogenase (Quinone)