A novel strategy toward developing CO prodrugs and its therapeutic applications

Developing organic prodrugs of gasotransmitters represent unique challenges. This is especially true with carbon monoxide, which does not have an easy u201chandleu201d for bioreversible derivatization. By taking advantage of intramolecular Diels-Alder reaction, we have developed a prodrug strategy for preparations of organic CO-prodrugs that are stable during synthesis and storage, and yet readily release CO with tunable release rates under near physiological conditions. The effectiveness of the CO-prodrug system in delivering a sufficient quantity of CO for possible therapeutic applications has been studied using cell culture anti-inflammatory assay and a colitis animal model. This study fully demonstrates the proof of concept, and lays foundation for further medicinal chemistry work in developing organic CO prodrugs.