Organic CO Prodrugs: Structure–CO‐Release Rate Relationship Studies

Pan, Zhixiang; Chittavong, Vayou; Li, Wei; Zhang, Jun; Ji, Kaili; Zhu, Mengyuan; Ji, Xiangming; Wang, Binghe

doi:10.1002/chem.201700936

Cited by 66 publications

(53 citation statements)

References 60 publications

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“…Therefore, novel water-soluble CO delivery molecules were described, tricarbonylchloro (glycinato) ruthenium II (RuCl(glycinato)(CO) 3 ), termed CORM-3; boron-based compound Na 2 H 3 BCO 2 , named CORM-A1; or recently developed CORM-401 (Mn(CO) 4 [43]) that in contrast to CORM-A1 releases up to three equivalents of CO per mol of the compound [42][43][44]. Additionally, the new class of organic CO-releasing prodrugs was developed recently [42,[45][46][47]. These CO prodrugs do not contain heavy metals, have a long half-life, and are able to release CO in a controllable manner.…”

Section: Carbon Monoxide Deliverymentioning

confidence: 99%

Carbon Monoxide Being Hydrogen Sulfide and Nitric Oxide Molecular Sibling, as Endogenous and Exogenous Modulator of Oxidative Stress and Antioxidative Mechanisms in the Digestive System

Korbut

Brzozowski

Magierowski

2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress reflects an imbalance between oxidants and antioxidants in favor of the oxidants capable of evoking tissue damage. Like hydrogen sulfide (H2S) and nitric oxide (NO), carbon monoxide (CO) is an endogenous gaseous mediator recently implicated in the physiology of the gastrointestinal (GI) tract. CO is produced in mammalian tissues as a byproduct of heme degradation catalyzed by the heme oxygenase (HO) enzymes. Among the three enzymatic isoforms, heme oxygenase-1 (HO-1) is induced under conditions of oxidative stress or tissue injury and plays a beneficial role in the mechanism of protection against inflammation, ischemia/reperfusion (I/R), and many other injuries. According to recently published data, increased endogenous CO production by inducible HO-1, its delivery by novel pharmacological CO-releasing agents, or even the direct inhalation of CO has been considered a promising alternative in future experimental and clinical therapies against various GI disorders. However, the exact mechanisms underlying behind these CO-mediated beneficial actions are not fully explained and experimental as well as clinical studies on the mechanism of CO-induced protection are awaited. For instance, in a variety of experimental models related to gastric mucosal damage, HO-1/CO pathway and CO-releasing agents seem to prevent gastric damage mainly by reduction of lipid peroxidation and/or increased level of enzymatic antioxidants, such as superoxide dismutase (SOD) or glutathione peroxidase (GPx). Many studies have also revealed that HO-1/CO can serve as a potential defensive pathway against oxidative stress observed in the liver and pancreas. Moreover, increased CO levels after treatment with CO donors have been reported to protect the gut against formation of acute GI lesions mainly by the regulation of reactive oxygen species (ROS) production and the antioxidative activity. In this review, we focused on the role of H2S and NO molecular sibling, CO/HO pathway, and therapeutic potential of CO-releasing pharmacological tools in the regulation of oxidative stress-induced damage within the GI tract with a special emphasis on the esophagus, stomach, and intestines and also two solid and important metabolic abdominal organs, the liver and pancreas.

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Section: Carbon Monoxide Deliverymentioning

confidence: 99%

Carbon Monoxide Being Hydrogen Sulfide and Nitric Oxide Molecular Sibling, as Endogenous and Exogenous Modulator of Oxidative Stress and Antioxidative Mechanisms in the Digestive System

Korbut

Brzozowski

Magierowski

2020

Oxidative Medicine and Cellular Longevity

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“…Wang and co‐workers have explored the development of organic prodrugs that undergo cheletropic reaction under physiologically relevant conditions to spontaneously release CO ,. These generally non‐toxic molecules (up to 100 μM) are designed to undergo inter‐ or intra‐molecular inverse electron demand Diels‐Alder (DA inv ) reactions with tunable CO release rates.…”

Section: Fluorescence Trackable Metal‐free Co‐releasing Molecules or mentioning

confidence: 99%

“…[24] The derivatives BW-CO-109 and BW-CO-117 were subsequently shown to exhibit a concentration-dependent increase in fluorescence intensity for CO delivery in RAW 264.7 cells. [36] A cascade drug delivery system (23, Figure 21) has also been developed on this premise wherein a drug payload (metronidazole) is released along with CO and a fluoranthene by-product. The latter provides visual evidence of the release of all three molecules.…”

Section: Click and Release Corms: Intra-and Inter-molecular Inverse Ementioning

confidence: 99%

“…Wang and co-workers have explored the development of organic prodrugs that undergo cheletropic reaction under physiologically relevant conditions to spontaneously release CO. [13,[36][37][38] These generally non-toxic molecules (up to 100 mM) are designed to undergo inter-or intra-molecular inverse electron demand Diels-Alder (DA inv ) reactions with tunable CO release rates. The unimolecular CO prodrugs (Figure 20) all undergo spontaneous CO release to produce fluorescent fluoranthene-containing products that can be tracked in cellular studies.…”

Section: Click and Release Corms: Intra-and Inter-molecular Inverse Ementioning

confidence: 99%

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Tracking CO Release in Cells via the Luminescence of Donor Molecules and/or their By‐Products

Soboleva

Berreau

2019

Israel Journal of Chemistry

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Carbon monoxide (CO) is a bioactive signalling molecule that is produced endogenously via the breakdown of heme. Beneficial health effects associated with the delivery of CO gas have spurred the development of CO‐releasing molecules (CORMs) that can be used to provide specific amounts of the gas. In addition to their potential use as therapeutics, CORMs are needed to provide insight into the biological targets of CO. In this regard, light‐activated CO‐releasing molecules (photoCORMs), are valuable for examining the effects of localized CO release. Herein we examine luminescent CORMs and photoCORMs that have been reported for tracking CO delivery in cells. A variety of motifs are available that exhibit differing luminescence properties and cover a wide range of wavelengths. Trackable CO donors have been successfully applied to targeting CO delivery to mitochondria, thus demonstrating the feasibility of using such molecules in detailed investigations of the biological roles of CO.

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“…The design for controlled CO release centers on conformational constraints, with an ester bond holding an alkyne dienophile away from a dienone. Upon cleavage of the ester bond by an esterase, the freed dienophile undergoes an entropically favored intramolecular Diels–Alder cycloaddition to release CO (Figure e; Ji et al, ; Pan et al, ). Proof‐of‐concept compounds readily release CO in the presence of PLE and give only the expected cyclization products in their respective reactions, suggesting that the enzyme‐catalyzed hydrolysis is the rate limiting step.…”

Section: Esterase‐activated Prodrugsmentioning

confidence: 99%

Microbial esterases and ester prodrugs: An unlikely marriage for combating antibiotic resistance

Larsen

Johnson

2018

Drug Development Research

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The rise of antibiotic resistance necessitates the search for new platforms for drug development. Prodrugs are common tools for overcoming drawbacks typically associated with drug formulation and delivery, with ester prodrugs providing a classic strategy for masking polar alcohol and carboxylic acid functionalities and improving cell permeability. Ester prodrugs are normally designed to have simple ester groups, as they are expected to be cleaved and reactivated by a wide spectrum of cellular esterases. However, a number of pathogenic and commensal microbial esterases have been found to possess significant substrate specificity and can play an unexpected role in drug metabolism. Ester protection can also introduce antimicrobial properties into previously nontoxic drugs through alterations in cell permeability or solubility. Finally, mutation to microbial esterases is a novel mechanism for the development of antibiotic resistance. In this review, we highlight the important pathogenic and xenobiotic functions of microbial esterases and discuss the development and application of ester prodrugs for targeting microbial infections and combating antibiotic resistance. Esterases are often overlooked as therapeutic targets. Yet, with the growing need to develop new antibiotics, a thorough understanding of the specificity and function of microbial esterases and their combined action with ester prodrug antibiotics will support the design of future therapeutics.

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Organic CO Prodrugs: Structure–CO‐Release Rate Relationship Studies

Cited by 66 publications

References 60 publications

Carbon Monoxide Being Hydrogen Sulfide and Nitric Oxide Molecular Sibling, as Endogenous and Exogenous Modulator of Oxidative Stress and Antioxidative Mechanisms in the Digestive System

Carbon Monoxide Being Hydrogen Sulfide and Nitric Oxide Molecular Sibling, as Endogenous and Exogenous Modulator of Oxidative Stress and Antioxidative Mechanisms in the Digestive System

Tracking CO Release in Cells via the Luminescence of Donor Molecules and/or their By‐Products

Microbial esterases and ester prodrugs: An unlikely marriage for combating antibiotic resistance

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