Redox-activated, hypoxia-selective DNA cleavage by quinoxaline 1,4-di-N-oxide

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作者：

B Ganley，G Chowdhury，J Bhansali，JS Daniels，KS Gates

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摘要：

Quinoxaline 1,4-dioxide () is the historical prototype for modern heterocyclic -oxide antitumor agents such as 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine, ) and 3-amino-2-quinoxalinecarbonitrile 1,4-dioxide (). Early experiments in bacterial cell lines suggested that enzymatic, single-electron reduction of quinoxaline 1,4-dioxides under low-oxygen (hypoxic) conditions leads to DNA damage. Here the ability of quinoxaline 1,4-dioxide to cleave DNA has been explicitly characterized using in vitro assays. The hypoxia-selective DNA-cleaving properties of reported here may provide a chemical basis for understanding the cytotoxic and mutagenic activities of various quinoxaline 1,4-dioxide antibiotics.The hypoxia-selective DNA-cleaving properties of quinoxaline 1,4-dioxide reported here may provide a chemical basis for understanding the cytotoxic and mutagenic activities of this compound as well as and other substituted quinoxaline 1,4-dioxide antibiotics.

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关键词：

cephalosporins aminoglycosides dual-action antibiotics toxicity antibacterials

DOI：

10.1016/S0968-0896(01)00163-8

被引量：

235

年份：

2001