The chemical reduction of diaziquone: products and free radical intermediates.
Sodium borohydride reduced diaziquone (AZQ) can cause cross-links between DNA molecules, between DNA and proteins and cause single- and double-strand DNA breaks. In order to understand these effects better, we investigated the reduction of diaziquone by borohydride, and looked at reaction products. We found that a major product was formed during the oxidation of the colorless 2-electron reduced AZQ, and that this product was a monoaziridinyl quinone. We interpret this result to mean that both the leaving aziridine as well as the remaining one can alkylate. This mode of alkylation does not explain cross-links which may occur by a different mechanism requiring simultaneous opening of the aziridine rings. Most of the antitumor activity of borohydride reduced AZQ is probably exerted during the oxidation of the 2-electron reduced AZQ (AZQH2).
Gutierrez
P L
PL
University of Maryland Cancer Center, Division of Developmental Therapeutics, Baltimore 21201.
Balachandran Nayar
M S
MS
Nardino
R
R
Callery
P S
PS
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D016227:Benzoquinones; D001894:Borohydrides; D002851:Chromatography, High Pressure Liquid; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D010084:Oxidation-Reduction; D013053:Spectrophotometry
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D016227:Benzoquinones; D001894:Borohydrides; D005609:Free Radicals; C029108:diaziquone