Mechanisms of action of quinone-containing alkylating agents: DNA alkylation by aziridinylquinones.
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.
Hargreaves
R H
RH
CRC Drug Development Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester, M20 4BX, U.K.
Hartley
J A
JA
Butler
J
J
D000478:Alkylation; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry* / Q000494:pharmacology*; D001388:Aziridines / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry; D016227:Benzoquinones / Q000737:chemistry; D002225:Carbazilquinone / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry; D006801:Humans; D045563:Indolequinones; D007211:Indoles / Q000737:chemistry; D016685:Mitomycin / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011809:Quinones / Q000737:chemistry*; D013329:Structure-Activity Relationship
D018906:Antineoplastic Agents, Alkylating; D001388:Aziridines; D001562:Benzimidazoles; D016227:Benzoquinones; D045563:Indolequinones; D007211:Indoles; D011809:Quinones; C071269:6-N-aziridinyl-3-hydrox-7-methyl-2,3-dihydro-1H-pyrrolo(1,2-a)benzimidazole-5,8-dione 3-acetate; C073715:2,5-dimethyl-3,6-diaziridinyl-1,4-benzoquinone; D002225:Carbazilquinone; D016685:Mitomycin; D004317:Doxorubicin; D004247:DNA; C029108:diaziquone; C060817:apaziquone