Redox reactions and cytotoxicity mechanisms of anticancer aziridinyl-substituted-1,4-benzoquinones: a minireview

Abstract

In this paper, we summarize the data on the cytotoxicity mechanisms of aziridinyl-substituted-1,4-benzoquinones, which are potentially important antitumor agents known since 1980s. High antitumor activity of aziridinyl-1,4-benzoquinones arises from the combined effects of their two-electron enzymatic reduction into aziridinyl-substituted hydroquinones which alkylate DNA more readily than the parent quinones, the oxidative stress-type cytotoxicity due to the redox cycling of the corresponding quinone free radicals, and the direct alkylation of DNA by the low-potential aziridinyl-benzoquinones. However, it may also cause the undesirable side-effects, i. e. their cytotoxicity in primary mammalian cells. In this context, including our recent findings, we aim to review: i) the redox properties of aziridinyl-1,4-benzoquinones, ii) their reactivity and structure-activity relationships in single- and two-electron reduction by flavoenzymes and related redox systems, iii) the structure-activity relationships in their cytotoxicity, and iv) the mechanisms of the cell death and the expression of signaling proteins under their action.