Norborn-2-en-7-ones as physiologically-triggered carbon monoxide-releasing prodrugs

Kueh, Jui Thiang Brian; Stanley, Nathan J; Hewitt, Russell J.; Woods, Laura M.; Larsen, Lesley; Harrison, Joanne C.; Rennison, David; Brimble, Margaret A.; Sammut, Ivan A.; Larsen, David S.

doi:10.1039/c7sc01647f

Cited by 64 publications

(53 citation statements)

References 40 publications

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“…It should be noted that the Larsen lab 237 and the Wang lab both reported prodrug systems that take advantage of this elimination approach for CO prodrug design. This approach allows for the synthesis of pH-, 185,237 ROS-, 188 and esterase-sensitive CO prodrugs. 187 It is also interesting to note that the release rate of the pH-sensitive ones can be adjusted based on the leaving group ability and can be quantitatively predicted using the Hammett constant of the substituents on the phenol leaving group.…”

Section: Author Manuscriptmentioning

confidence: 99%

“…Larson and coworkers have reported an approach based on norborn-2-en-7-one chemistry (1). 238 The elimination of the HBr under basic conditions results in the formation of the norbornadienone, which undergo cheletropic loss of CO and aromatization to form the byproduct. Compound 1 showed in-vitro vascular dilatory effects with an EC 50 of about 1.6 μM.…”

Section: Author Manuscriptmentioning

confidence: 99%

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Carbon monoxide: An emerging therapy for acute kidney injury

Yang

Caestecker

Otterbein

et al. 2019

Medicinal Research Reviews

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Treating acute kidney injury (AKI) represents an important unmet medical need both in terms of the seriousness of this medical problem and the number of patients. There is also a large untapped market opportunity in treating AKI. Over the years, there has been much effort in search of therapeutics with minimal success. However, over the same time period, new understanding of the underlying pathobiology and molecular mechanisms of kidney injury have undoubtedly helped the search for new therapeutics. Along this line, carbon monoxide (CO) has emerged as a promising therapeutic agent because of its demonstrated cytoprotective, and immunomodulatory effects. CO has also been shown to sensitize cancer, but not normal cells, to chemotherapy. This is particularly important in treating cisplatin-This is the author manuscript accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

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Section: Author Manuscriptmentioning

confidence: 99%

Section: Author Manuscriptmentioning

confidence: 99%

Carbon monoxide: An emerging therapy for acute kidney injury

Yang

Caestecker

Otterbein

et al. 2019

Medicinal Research Reviews

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“…to behave as a thermal-CORM. [9,23] The HCD data is included in Section S5, along with a detailed discussion of the various HCD channels. Figure 3 illustrates the observed [MnL(CO)3(CH3CN)]•H + fragmentation pathways.…”

Section: Thermal Fragmentation Pathways Of [Mnl(co)3(ch3cn)]•h + and mentioning

confidence: 99%

Direct Measurement of the Visible to UV Photodissociation Processes for the PhotoCORM TryptoCORM

Cercola¹,

Fischer²,

Scherman³

et al. 2019

Preprint

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We apply laser photodissociation spectroscopy in the gas phase to TryptoCORM, a known photoCORM that has been shown to destroy <i>Escherichia coli</i> upon visible-light activation. Our experiments allow us to fully map TryptoCORM’s photochemistry across a wide wavelength range by using novel laser-interfaced mass spectrometry (LIMS). We complement these measurements with Cryogenic Ion Vibrational Spectroscopy (CIVS), to structurally characterise gaseous TryptoCORM.

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“…There are different ways to disintegrate CORMs/CORMats for the release of CO moiety by means of; peculiar physiological conditions [52], trigger by temperature [53], activation by an enzyme [54], pH alteration and increase in reactive oxygen species (ROS) concentration, accessibility to distinct wavelength of light [55,56], either using thermal degradation or ligand exchange/substitution or both [53] and prototypically activation through oxidation mechanism [11,57,58]. In order to deliver the CO molecules at a specified therapeutic rate, it is necessary to characterize the CORMs and CORMats entities, as quantification of such mechanisms might be contingent with its physical conditions like O 2 , temperature, assay solution and light conditions.…”

Section: Introductionmentioning

confidence: 99%

CO-Releasing Materials: An Emphasis on Therapeutic Implications, as Release and Subsequent Cytotoxicity Are the Part of Therapy

et al. 2019

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The CO-releasing materials (CORMats) are used as substances for producing CO molecules for therapeutic purposes. Carbon monoxide (CO) imparts toxic effects to biological organisms at higher concentration. If this characteristic is utilized in a controlled manner, it can act as a cell-signaling agent for important pathological and pharmacokinetic functions; hence offering many new applications and treatments. Recently, research on therapeutic applications using the CO treatment has gained much attention due to its nontoxic nature, and its injection into the human body using several conjugate systems. Mainly, there are two types of CO insertion techniques into the human body, i.e., direct and indirect CO insertion. Indirect CO insertion offers an advantage of avoiding toxicity as compared to direct CO insertion. For the indirect CO inhalation method, developers are facing certain problems, such as its inability to achieve the specific cellular targets and how to control the dosage of CO. To address these issues, researchers have adopted alternative strategies regarded as CO-releasing molecules (CORMs). CO is covalently attached with metal carbonyl complexes (MCCs), which generate various CORMs such as CORM-1, CORM-2, CORM-3, ALF492, CORM-A1 and ALF186. When these molecules are inserted into the human body, CO is released from these compounds at a controlled rate under certain conditions or/and triggers. Such reactions are helpful in achieving cellular level targets with a controlled release of the CO amount. However on the other hand, CORMs also produce a metal residue (termed as i-CORMs) upon degradation that can initiate harmful toxic activity inside the body. To improve the performance of the CO precursor with the restricted development of i-CORMs, several new CORMats have been developed such as micellization, peptide, vitamins, MOFs, polymerization, nanoparticles, protein, metallodendrimer, nanosheet and nanodiamond, etc. In this review article, we shall describe modern ways of CO administration; focusing primarily on exclusive features of CORM’s tissue accumulations and their toxicities. This report also elaborates on the kinetic profile of the CO gas. The comprehension of developmental phases of CORMats shall be useful for exploring the ideal CO therapeutic drugs in the future of medical sciences.

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Norborn-2-en-7-ones as physiologically-triggered carbon monoxide-releasing prodrugs

Abstract: A prodrug strategy for the release of the gasotransmitter carbon monoxide (CO) at physiological pH, based upon 3a-bromo-norborn-2-en-7-one Diels–Alder cycloadducts has been developed.

Cited by 64 publications

References 40 publications

Carbon monoxide: An emerging therapy for acute kidney injury

Carbon monoxide: An emerging therapy for acute kidney injury

Direct Measurement of the Visible to UV Photodissociation Processes for the PhotoCORM TryptoCORM

CO-Releasing Materials: An Emphasis on Therapeutic Implications, as Release and Subsequent Cytotoxicity Are the Part of Therapy

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