CO and CO-Releasing Molecules in Medicinal Chemistry

Abstract

Since the discovery that CO acts as a cytoprotective and homeostatic molecule, increasing research efforts have been devoted to the exploitation of its therapeutic effects. Both endogenous and exogenous CO improves experimental lung, vascular and cardiac injuries and protects against several inflammatory states. The technology is now in place to bring CO to clinical applications, but the use of the gaseous molecule poses several problems. The challenges associated with the clinical implementation of the gas have in part been answered by the development of CO-releasing molecules (CO-RMs). As stable solid forms of CO, these molecules represent an alternative to the administration of carbon monoxide (orally or by injection). In this article, we present insights into the biochemical action of CO and discuss the efficacy of CO and CO-RMs in preclinical disease models. Recent advances in the CO-RMs field are critically addressed.

Modified biovectors for the tuneable activation of anti-platelet carbon monoxide release

“…Unlike most common drugs whose pharmacological action is dependent on their interaction with a macromolecular target and whose potency is dictated by the stability of the drug-target complex, CORMs exert their therapeutic action via the liberated CO molecules. [1][2][3][4][5] However, apart from the common scientific consensus that CORM-based therapy should not lead to significant carboxyhemoglobin (COHb) formation and to the inhibition of respiratory enzymes that are sensitive to CO, it is questionable whether CORMs should release CO slowly or rapidly and what kinetics of CO release is most advantageous for therapeutic applications. There are only few reports clearly showing the advantages of CORMs slowly releasing CO over those releasing CO instantly 6,7 and they relate to the anti-platelet effects of CORMs.…”

The role of gasotransmitters NO, H2S and CO in myocardial ischaemia/reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning

“…The facial tricarbonyl fac-[RuCl(glycinate)(CO)3], often referred to as CORM-3, is the prototypical water-soluble CORM in this area (Chatterjee, 2004;Johnson et al, 2007). Details of CO donors (Romão et al 2012;, Zobi, 2013;Gonzales and Mascharak, 2014) and an excellent methodological review on measurement techniques of CO (Motterlini and Otterbein, 2010) are available. Such molecules confer cardioprotection both in ex vivo and in vivo experiments.…”

PhotoCORMs: CO release moves into the visible

“…There has therefore been significant effort to produce molecules which can release CO, so-called CORMs (carbon monoxide releasing molecules). [16][17][18][19][20] The majority of these systems are based around metal carbonyl fragments, which offer a direct route to the release of CO. Such organometallic therapeutics are unusual, and efforts have been made to exploit alternative CO sources.…”