Mechanisms of action of quinone-containing alkylating agents: DNA alkylation by aziridinylquinones

Front Biosci. 2000 Nov 1:5:E172-80. doi: 10.2741/hargreav.

Abstract

Aziridinyl quinones can be activated by cellular reductases eg. DT-diaphorase and cytochrome P450 reductase to form highly reactive DNA alkylating agents. The mechanisms by which this activation and alkylation take place are many and varied. Using clinically relevant and experimental agents this review will describe many of these mechanisms. The agents discussed are Mitomycin C, EO9 and analogues, diaziridinylbenzoquinones and the pyrrolo[1, 2-alpha]benzimidazolequinones.

Publication types

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

MeSH terms

  • Alkylation
  • Antineoplastic Agents, Alkylating / chemistry*
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Aziridines / chemistry*
  • Benzimidazoles / chemistry
  • Benzoquinones / chemistry
  • Carbazilquinone / chemistry
  • DNA / chemistry*
  • Doxorubicin / chemistry
  • Humans
  • Indolequinones*
  • Indoles / chemistry
  • Mitomycin / chemistry
  • Molecular Structure
  • Oxidation-Reduction
  • Quinones / chemistry*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Alkylating
  • Aziridines
  • Benzimidazoles
  • Benzoquinones
  • Indolequinones
  • Indoles
  • Quinones
  • 6-N-aziridinyl-3-hydrox-7-methyl-2,3-dihydro-1H-pyrrolo(1,2-a)benzimidazole-5,8-dione 3-acetate
  • 2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone
  • Carbazilquinone
  • Mitomycin
  • Doxorubicin
  • DNA
  • diaziquone
  • apaziquone