Mode of action of anti-infective agents: Focus on oxidative stress and electron transfer

There is increasing evidence for involvement of oxidative stress (OS) in the mechanism of action of a wide variety of physiologically active materials. Often the reactive oxygen species (ROS) are generated by electron transfer (ET) or other routes mediated by free radicals. Principal ET functionalities are quinones (or precursors), metal complexes, aromatic nitro compounds (ArNO2), and conjugated imines. These moieties are commonly found in the structures of anti-infective agents or their metabolites. In most cases, the ET functionalities display reduction potentials in the physiologically active range, i.e. more positive than approximately -0.5 V. Though the focus of this review is on OS and ET, a mode of action which emulates the natural immune system of the host, in some cases, this mechanism also appears to be involved in more generally accepted approaches, such as enzyme inhibition, adverse effects on membranes and DNA, or interference with DNA or protein synthesis. OS-ET represents a broad understanding of drug action that can aid in the design of new antiinfective agents. It is significant that a relatively simple unifying theme can be applied not only to the action of the predominant groups of anti-infective agents, but also more generally to other drug classes, toxins, carcinogens, enzymes, and hormones.