Adapting decarbonylation chemistry for the development of prodrugs capable of in vivo delivery of carbon monoxide utilizing sweeteners as carrier molecules

Abstract

Carbon monoxide as an endogenous signaling molecule exhibits pharmacological efficacy in various animal models of organ injury. To address the difficulty in using CO gas as a therapeutic agent for...

De Novo Construction of Fluorophores via CO Insertion-Initiated Lactamization: A Chemical Strategy toward Highly Sensitive and Highly Selective Turn-On Fluorescent Probes for Carbon Monoxide

“…There have been extensive studies of the physiological and pharmacological roles of CO. − CO is produced endogenously in the human body under normal physiological conditions primely through heme oxygenase-mediated degradation of heme, with a concentration in the blood in the mid micromolar range . CO exerts anti-inflammatory and cyto- and organ-protective effects. ,− For example, it offers protection in lipopolysaccharide-induced inflammation, ischemia–reperfusion injuries, , and chemically , and rhabdomyolysis -induced organ injuries. The prospect of developing CO into a therapeutic agent for colitis, sickle cell disease, and acute kidney injury, among others, , is supported by the corresponding animal model studies.…”

“…The prospect of developing CO into a therapeutic agent for colitis, sickle cell disease, and acute kidney injury, among others, , is supported by the corresponding animal model studies. Extensive efforts have been made in recent years in evaluating inhaled CO gas in clinical trials, , developing non-gaseous CO delivery approaches, including liquid and foam formulations, metal-based CO-releasing molecules (CORMs), ,, and organic light-activated CORMs, − organic prodrugs, ,− and their formulations . A unique challenge to studying the dose–response relationship of CO is the lack of facile methods for the sensitive and selective determination of its concentration in the blood and various tissues. − Along this line, there is still much to be desired from existing methods.…”

“…7 CO exerts anti-inflammatory and cyto-and organ-protective effects. 3,8−10 For example, it offers protection in lipopolysaccharide-induced inflammation, 11 ischemia−reperfusion injuries, 12,13 and chemically 14,15 and rhabdomyolysis 16 -induced organ injuries. The prospect of developing CO into a therapeutic agent for colitis, 17 sickle cell disease, 18 and acute kidney injury, 19 among others, 8,20 is supported by the corresponding animal model studies.…”

“…For improved sensitivity and selectivity to enable CO quantification in biologically relevant samples and to facilitate our undergoing development of CO-based therapies, ,,,, we are interested in developing new chemical strategies for CO fluorescence probes. Our design is based on fluorescence turn-on via de novo fluorophore construction for fast, sensitive, and selective (actually exclusive) detection of CO with a high SNR.…”

ItaCORMs: conjugation with a CO-releasing unit greatly enhances the anti-inflammatory activity of itaconates

“… 7 To avoid the risks and toxicity associated with administration of CO by inhalation, the development of methods for the targeted delivery of CO, particularly through the use of CO-releasing molecules (CORMs), has become a fascinating field of drug discovery. 8 While a variety of CORMs have been reported in the literature, most of them do not meet the requirements for pharmaceutical application. A promising concept to meet the challenge of controlled (intracellular) CO release is the use of enzyme-triggered CORMs (ET-CORMs).…”