N-Nitrosamine-{cis-Re[CO]<sub>2</sub>}<sup>2+</sup> cobalamin conjugates as mixed CO/NO-releasing molecules

Santoro, Giuseppe; Beltrami, Ruben; Kottelat, Emmanuel; Blacque, Olivier; Bogdanova, Anna; Zobi, Fabio

doi:10.1039/c5dt03402g

Cited by 22 publications

(16 citation statements)

References 51 publications

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“…It is unclear to us at the present stage why or how the ethynyl-α-diimine ligands influence the anticancer activity of the molecules and render the CO-depleted metal fragments of Mn-2 and B 12 -Mn-2 active. We have previously shown that, e.g., NO release of organic N-nitrosamine is activated if the molecules are in contact with cultured cells [53]. Here perhaps a similar slow activation is at play for these photoCORMs.…”

Section: Discussionmentioning

confidence: 88%

Cytotoxicity of Mn-based photoCORMs of ethynyl-α-diimine ligands against different cancer cell lines: The key role of CO-depleted metal fragments

Rossier

Delasoie

Haeni

et al. 2020

Journal of Inorganic Biochemistry

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A series of tricarbonyl manganese complexes bearing 4-ethynyl-2,2′-bipyridine and 5-ethynyl-1,10-phenanthroline α-diimine ligands were synthetized, characterized and conjugated to vitamin B 12 , previously used as a vector for drug delivery, to take advantage of its water solubility and specificity toward cancer cells. The compounds act as photoactivatable carbon monoxide-releasing molecules rapidly liberating on average ca. 2.3 equivalents of CO upon photo-irradiation. Complexes and conjugates were tested for their anticancer effects, both in the dark and following photo-activation, against breast cancer MCF-7, lung carcinoma A549 and colon adenocarcinoma HT29 cell lines as well as immortalized human bronchial epithelial cells 16HBE14o-as the noncarcinogenic control. Our results indicate that the light-induced cytotoxicity these molecules can be attributed to both their released CO and to their CO-depleted metal fragments including liberated ligands.

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Section: Discussionmentioning

confidence: 88%

Cytotoxicity of Mn-based photoCORMs of ethynyl-α-diimine ligands against different cancer cell lines: The key role of CO-depleted metal fragments

Rossier

Delasoie

Haeni

et al. 2020

Journal of Inorganic Biochemistry

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“…Zobi and coworkers used (CN)Cbl as a scaffold for carbon monoxide CO‐releasing complexes ,,. By functionalizing cobalamin both at the ribose and at β‐axial position they obtained mixed CO/NO‐releasing molecules (Scheme ) . To this end, cobalamin was firstly functionalized at the R 5′ ‐OH group with a macrocyclic amine (compounds 45 a – c ) and subsequently treated with NaNO 2 (compounds 46 a – c ).…”

Section: Double‐conjugated Cobalaminsmentioning

confidence: 99%

“…To this end, cobalamin was firstly functionalized at the R 5′ ‐OH group with a macrocyclic amine (compounds 45 a – c ) and subsequently treated with NaNO 2 (compounds 46 a – c ). The resulting N ‐nitrosamine cobalamins 46 a – c were reacted with [Et 4 N] 2 [Re II (CO) 2 Br 4 ] furnishing derivatives 47 a – c which were found to liberate CO and small doses of NO in buffer solutions and exhibited cytoprotection in an ischemia‐reperfusion model …”

Section: Double‐conjugated Cobalaminsmentioning

confidence: 99%

Synthetic Approaches toward Vitamin B₁₂ Conjugates

2018

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The ability to conjugate functional molecules to vitamin B 12 (cobalamin) is an important strategy for the construction of hybrid molecules with various applications in medicinal chemistry, diagnostics, and biological sciences. Cobalamin, as an exogenous compound, reaches mammalian cells via a system of transport proteins and therefore the position of conjugation must be selected in such a way that the recognition process is not disturbed. The complex structure of vitamin B 12 provides many routes for the synthesis of conjugates containing cargos appended at different sites, however, only the e-propionamide chain, βaxial position and R 5' -OH are found to meet the aforementioned criteria. Over the years, a number of synthetic approaches leading to cobalamin conjugates have been developed and, herein, we summarize those leading to conjugates with a cargo tethered at the central cobalt ion, macrocyclic core, ribonucleotide moiety, or a combination thereof. . Synthesis of cobalamin triazoles. Scheme 16. Synthesis of precursor 41 and its subsequent functionalization. Scheme 17. Functionalization of phosphate moiety.[a] Compound 43 c was obtained from 43 b via substitution with NaN 3 .

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“…Recent research efforts by other groups towards developing water-soluble photoCORMs have employed different appendages to the car-bonyl complexes to improve their solubility. For example, Schatzschneider and co-workers have reported a peptide appended photoCORM, 41 while Zobi and co-workers have attached photoCORMs to vitamin B 12 platform 42,43 to achieve solubility in aqueous media. In this report, complex 2 represents a new class of highly water-soluble photoCORM with a much simpler design and straightforward synthetic strategy.…”

Section: Resultsmentioning

confidence: 99%

Light-triggered CO delivery by a water-soluble and biocompatible manganese photoCORM

et al. 2016

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The discovery of salutary effects of low doses of carbon monoxide (CO) has spurred interest in designing exogenous molecules that can deliver CO to biological targets under controlled conditions. Herein we report a water-soluble photosensitive manganese carbonyl complex [MnBr(CO)3(pyTAm)] (2) (pyTAm = 2-(pyridyl)imino-triazaadamantane) that can be triggered to release CO upon exposure to visible light. Inclusion of a triazaadamantyl pharmacophore into the coligand of 2 improves its stability and solubility in water. Change in the coligand from 2-(pyridyl)imino-triazaadamantane to 2-(pyridyl)iminoadamantane (pyAm) or 2-(quinonyl)imino-triazaadamantane (qyTAm) dramatically alters these desired properties of the photoCORM. In addition to structures and CO-releasing properties of the three analogous complexes 1–3 from these three α-diimine ligands, theoretical calculations have been performed to determine the origin of Mn–CO bond labilization upon illumination. Rapid delivery of CO to myoglobin under physiological conditions attests the potential of 2 as a biocompatible photoCORM.

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N-Nitrosamine-{cis-Re[CO]₂}²⁺ cobalamin conjugates as mixed CO/NO-releasing molecules

Cited by 22 publications

References 51 publications

Cytotoxicity of Mn-based photoCORMs of ethynyl-α-diimine ligands against different cancer cell lines: The key role of CO-depleted metal fragments

Cytotoxicity of Mn-based photoCORMs of ethynyl-α-diimine ligands against different cancer cell lines: The key role of CO-depleted metal fragments

Synthetic Approaches toward Vitamin B₁₂ Conjugates

Light-triggered CO delivery by a water-soluble and biocompatible manganese photoCORM

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N-Nitrosamine-{cis-Re[CO]2}2+ cobalamin conjugates as mixed CO/NO-releasing molecules

Cited by 22 publications

References 51 publications

Cytotoxicity of Mn-based photoCORMs of ethynyl-α-diimine ligands against different cancer cell lines: The key role of CO-depleted metal fragments

Cytotoxicity of Mn-based photoCORMs of ethynyl-α-diimine ligands against different cancer cell lines: The key role of CO-depleted metal fragments

Synthetic Approaches toward Vitamin B12 Conjugates

Light-triggered CO delivery by a water-soluble and biocompatible manganese photoCORM

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Product

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N-Nitrosamine-{cis-Re[CO]₂}²⁺ cobalamin conjugates as mixed CO/NO-releasing molecules

Synthetic Approaches toward Vitamin B₁₂ Conjugates