Diane K. Smith, T. Andres, M. Horton
Mar 8, 2013
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Abstract
A number of nitroimidazoles (NI’s) are used as drugs to treat a variety of infections by anaerobic microorganisms. In all cases the NI’s are believed to require in vivo reduction in order to be activated. However, the actual active forms of the drugs as well as the mechanisms of action are not known for certain. One widely accepted theory is that the active form is a 1 e reduction product, either the radical anion or the protonated radical, which causes cell death by inflicting extensive damage to the organism’s DNA. Other research suggests that it may be the 2 e product, the nitroso, that is the active species. Nitrosobenzenes are known to react with thiols like glutathione and cysteine in vitro and in vivo. Thus an alternative hypothesis is that cell death is caused by deactivation of key proteins and/or the disturbance of cellular redox balance due to adduct formation between the NI and cysteine residues.