Studies on the Mechanism of Activation and the Mutagenicity of Ronidazole, a 5-Nitroimidazole
5-Nitroimidazoles are used for treating protozoal and bacterial diseases in man and in animals and for potentiating the effects of chemo-and radiation therapy (Lossick, 1982; Goldman, 1980; Muller, 1981; Chessin, et al.,1978). They possess the unique property of requiring low oxygen tension in order for productive enzymatic nitro reduction to occur. This property is especially advantageous for the expression of therapeutic activity under anaerobic or hypoxic conditions such as against anaerobes and solid tumors. The presence of oxygen causes the reoxidation of a one electron reduced product, the nitroanion radical, back to the parent nitroimidazole and, consequently, results in the redox cycling of the drug and the generation of superoxide anion under hypoxie conditions. Since nitro reduction is an obligatory step for the biological activities of these drugs, the redox cycling may represent either a futile pathway in the activation of this drug or a mechanism for potentiating the activity of the nitroimidazole if a product of the superoxide anion underlies these activities.
KeywordsMutagenic Activity Nucleophilic Addition Redox Cycling Residual Drug Cysteine Thiol
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