Mechanistic Insights and Pharmacological Approaches for Nitrogen and Sulfur Mustards and Their Implications as Therapeutic Agents

Nitrogen and sulfur mustards, often acting as vesicants, have significant consequences for public health. Skin is a common site for exposure to these vesicants that can result in considerable morbidity and mortality. Given that the treatment options are limited, new insights into the mechanisms for the toxicity of these vesicants that can be translated into preventative/therapeutic strategies are desperately needed. Importantly, like most antineoplastic agents, including chemotherapy, the cytotoxic activity of vesicants such as nitrogen mustard (i.e., mustargen/mechlorethamine) and sulfur mustard is primarily mediated via their ability to act as alkylating agents. The current review highlights the underlying mechanisms, effects as well as approaches to mitigate sulfur and nitrogen mustard-induced effects, and their potential to be explored as therapeutic agents. Insights into the mediating roles and impacts of mustard agents could lead to future research and interventions that raise public health awareness to circumvent their adverse events and exploit desirable effects against proliferative diseases such as cancer.