Nitric oxide, hydrogen sulfide and carbon monoxide are all very toxic molecules, and yet they belong to the gasotransmitter family of signaling molecules with importance on par with that of neurotransmitters and hormone molecules. Among these gasotransmitters, carbon monoxide has shown pleotropic cytoprotective and anti-inflammatory effects in animal models of colitis, kidney reperfusion injury, traumatic brain injury, heart ischemia reperfusion injury, sepsis, among others. A major hurdle in developing CO-based therapeutics is the development of pharmaceutically acceptable forms of delivery since earlier work had largely relied on gaseous CO and CO in metal complexes referred to as carbon monoxide-releasing molecules (CORMs). This presentation will discuss the development of different structural classes of carbon monoxide prodrugs by using unique biorthogonal reactions. Such CO prodrugs have tunable release rates, and can respond to signals such as pH, reactive oxygen species, esterases, and concentration. The pharmacologic effects on select prodrugs have been validated in animal models of colitis, systemic inflammation, kidney reperfusion injury, among others.

Click and release: Unique approach to prodrugs of gasotransmitters

2019 Fall National Meeting

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