Novel, unifying mechanism for aromatic primary-amines (therapeutics, carcinogens and toxins): electron transfer, reactive oxygen species, oxidative stress and metabolites

Aromatic primary-amines (APAs) display physiological activity in various areas, including therapeutics, carcinogens and toxicants. More familiar examples include aniline and derivatives, naphthylamines, dapsone, sulfa drugs and procaineamide. Diverse mechanisms have been proposed for these agents. However, there has not been recognition for a unifying theme entailing electron transfer (ET), reactive oxygen species (ROS) and oxidative stress (OS). Prior reviews demonstrate that the ET-ROS-OS theme can be applied to therapeutics, carcinogens and toxicants. The preponderance of bioactive substances or their metabolites incorporate ET functionalities, which, we believe, play an important role in physiological responses. Among these, the focus in the present review is on APAs which generate ET hydroxylamine and nitroso metabolites which can generate ROS via redox cycling. Evidence suggests involvement of the metabolites in the bioactivity. Further support is provided by AO protection of toxicity which supports involvement of ROS. Apparently, a multifaceted approach best pertains.