Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics

Seixas, João; Mukhopadhyay, Abhik; Santos‐Silva, Teresa; Otterbein, Leo E.; Gallo, David; Rodrigues, Sandra; Guerreiro, Bruno; Gonçalves, Aldina; Penacho, Nuno; Marques, Ana Rita; Coelho, Ana C.; Reis, Patrícia M.; Romão, Maria João; Romão, Carlos C.

doi:10.1039/c2dt32174b

Cited by 70 publications

(51 citation statements)

References 54 publications

(118 reference statements)

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“…It turned out that isonitriles were the ligands of choice, and the correct selection of peripheral functional groups indeed led to the desired tissue selectivity. Furthermore, for a related molybdenum(0) compound, Na[Mo(histidinate)(CO) 3 ], it was shown that this is finally metabolized to a polyoxomolybdate cluster [PMo 12 O 40 ] 3− , as demonstrated by X‐ray crystallography of this species bound to lysozyme (Seixas et al ., ). Thus, instead of somewhat arbitrarily preparing and screening further metal carbonyl complexes, there is a very clear need for compounds that are designed for a very particular biomedical application and thoroughly examined not only for their CO release behaviour, but also the follow‐up products.…”

Section: Corms: Important Lead Structures and Novel Developmentsmentioning

confidence: 97%

Novel lead structures and activation mechanisms for CO‐releasing molecules (CORMs)

Schatzschneider

2014

British J Pharmacology

231

190

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Carbon monoxide (CO) is an endogenous small signalling molecule in the human body, produced by the action of haem oxygenase on haem. Since it is very difficult to apply safely as a gas, solid storage and delivery forms for CO are now explored. Most of these CO-releasing molecules (CORMs) are based on the inactivation of the CO by coordinating it to a transition metal centre in a prodrug approach. After a brief look at the potential cellular target structures of CO, an overview of the design principles and activation mechanisms for CO release from a metal coordination sphere is given. Endogenous and exogenous triggers discussed include ligand exchange reactions with medium, enzymatically-induced CO release and photoactivated liberation of CO. Furthermore, the attachment of CORMs to hard and soft nanomaterials to confer additional target specificity to such systems is critically assessed. A survey of analytical methods for the study of the stoichiometry and kinetics of CO release, as well as the tracking of CO in living systems by using fluorescent probes, concludes this review. CORMs are very valuable tools for studying CO bioactivity and might lead to new drug candidates; however, in the design of future generations of CORMs, particular attention has to be paid to their drug-likeness and the tuning of the peripheral 'drug sphere' for specific biomedical applications. Further progress in this field will thus critically depend on a close interaction between synthetic chemists and researchers exploring the physiological effects and therapeutic applications of CO. LINKED ARTICLESThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10. 1111/bph.2015.172.issue-6 Abbreviations BODIPY, boron dipyrromethene difluoride; CORM, CO-releasing molecule; EPR, electron paramagnetic resonance; ET-CORM, enzyme-triggered CORM; HO, haem oxygenase; Mb, myoglobin; MbCO, carboxymyoglobin; MO, molecular orbital; MOF, metal-organic framework; PhotoCORM, photoactivatable CORM; sGC, soluble guanylate cyclase; YFP, yellow fluorescent protein Carbon monoxide: a small signalling molecule with specific target structuresCarbon monoxide (CO) is now well established as the third small signalling molecule in higher organisms, including humans (Wu and Wang, 2005;Kim et al., 2006;Piantadosi, 2008). It is endogenously generated by the action of haem oxygenase (HO) on haem (see Alexander et al., 2013c), which also leads to the formation of iron(II) and biliverdin. The latter is further converted to bilirubin by biliverdin reductase. The enzymatic mechanism has been elucidated at the molecular level by a combination of spectroscopic and BJP British Journal of Pharmacology DOI:10.1111/bph.12688 www.brjpharmacol.org 1638 British Journal of Pharmacology (2015) 172 1638-1650© 2014 The British Pharmacological Society theoretical approaches (Chen et al., 2008;Lai et al., 2010;Matsui et al., 2010) as well as X-ray crystal structure analysis (Friedman et al.,...

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Section: Corms: Important Lead Structures and Novel Developmentsmentioning

confidence: 97%

Novel lead structures and activation mechanisms for CO‐releasing molecules (CORMs)

Schatzschneider

2014

British J Pharmacology

231

190

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“…After CO release and ligand dissociation, cascades followed by oxidation processes, molybdenum-based CORMs end up as phosphomolybdate [PMo 12 O 40 ] 3− ; an X-ray structure determination showed the adduct formation of this anion with lysozyme via a hydrogen-bridge network. 170 …”

Section: Controlled Release Of Comentioning

confidence: 99%

Carbon monoxide – physiology, detection and controlled release

et al. 2014

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Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs, are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed.

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“…However, few studies have assessed this matter. The complex fac ‐Na[Mo(histidinato)(CO) 3 ] (ALF186) has proven to be a good model for the study of some fundamental interactions of organometallic complexes with biological media 38. Triggered by O 2 , ALF186 immediately releases all of its CO equivalents, which are then transported in the systemic circulation, bound or unbound, to hemoglobin.…”

Section: Current Limitations For the Clinical Use Of Cormsmentioning

confidence: 99%

Carbon‐Monoxide‐Releasing Molecules for the Delivery of Therapeutic CO In Vivo

2014

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The development of carbon-monoxide-releasing molecules (CORMs) as pharmaceutical agents represents an attractive and safer alternative to administration of gaseous CO. Most CORMs developed to date are transition-metal carbonyl complexes. Although such CORMs have showed promising results in the treatment of a number of animal models of disease, they still lack the necessary attributes for clinical development. Described in this Minireview are the methods used for CORM selection, to date, and how new insights into the reactivity of metal-carbonyl complexes in vivo, together with advances in methods for live-cell CO detection, are driving the design and synthesis of new CORMs, CORMs that will enable controlled CO release in vivo in a spatial and temporal manner without affecting oxygen transport by hemoglobin.

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Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics

Cited by 70 publications

References 54 publications

Novel lead structures and activation mechanisms for CO‐releasing molecules (CORMs)

Novel lead structures and activation mechanisms for CO‐releasing molecules (CORMs)

Carbon monoxide – physiology, detection and controlled release

Carbon‐Monoxide‐Releasing Molecules for the Delivery of Therapeutic CO In Vivo

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