Organoselenium compounds as redox modulators of inflammation: Synthetic strategies, mechanistic insights, and therapeutic potential.

Abstract

Inflammation is a fundamental biological response, whose chronic activation contributes to the development and progression of numerous diseases, including arthritis, cardiovascular and neurodegenerative disorders. As such, the discovery of safe and effective anti-inflammatory drugs remains a central challenge in medicinal chemistry. Oxidative stress is a key pathological driver of chronic inflammation, promoting the overproduction of pro-inflammatory mediators through the activation of redox-sensitive transcription factors such as NF-κB and AP-1. This bidirectional relationship has attracted interest towards compounds that target both oxidative stress and inflammation. In this scenario, selenium is well known for its role in redox regulation through incorporation into selenoproteins like glutathione peroxidase. Inspired by this biology, a broad array of selenium-containing small molecules has been developed to exploit both antioxidant and anti-inflammatory activities. These compounds have shown the ability to modulate oxidative pathways, suppress inflammatory cytokines, and inhibit COX-2 expression in various disease models. The chemical versatility of selenium enables its incorporation into diverse scaffolds, offering - in some cases - a rewarding strategy to achieve enhanced pharmacological profiles, improved bioavailability, and reduced toxicity compared to classical anti-inflammatory agents. This review covers recent advances in the design, synthesis, and biological evaluation of selenium-based small molecules with anti-inflammatory properties, highlighting their potential as next-generation therapeutic agents.