Towards Gaseous Mediator Hybrid Drugs

Abstract In the past three decades, considerable progress has been made in the identification and characterization of three gaseous mediators now understood to be ubiquitous in mammalian biology: nitric oxide (NO), hydrogen sulfide (H 2 S), and carbon monoxide (CO). At low concentration these share a cytoprotective/antiinflammatory effect but cause cell death at high concentration. The first property is relevant to the treatment of inflammatory disorders and acute conditions, the second to cancer and antimicrobial therapy. The nonspecific but generally benign perception of their actions has made donor groups for the gaseous mediators attractive for incorporation into a large range of drug types. This chapter provides a brief overview of the biology of NO, H 2 S, and CO as well as a review of the chemistry of NO and H 2 S donors and their application in hybrid drug design, with a focus on NSAID and aspirin hybrid design and on findings from clinical studies.