Aminoferrocene‐Based Anticancer Prodrugs Labelled with Cyanine Dyes for in vivo Imaging

Özkan, Hülya Gizem; Toms, Johannes; Maschauer, Simone; Prante, Olaf; Mokhir, Andriy

doi:10.1002/ejic.202100829

Cited by 7 publications

(3 citation statements)

References 16 publications

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“…Looking at the results of the antioxidant activity of their lower homologues 6, 8, 10, 12, 14, and 16 (Table 9), the introduction of an additional hydrophobic amino acid did not contribute to the improvement of the antioxidant activity. 0.62 ± 0.15 88.68 ± 24.52 Ac-L-Leu-NH-Fn-NH-L-Leu-Boc (21) 0.56 ± 0.17 81.98 ± 7.04 Ac-D-Leu-NH-Fn-NH-D-Leu-Boc (22) 0.60 ± 0.10 122.75 ± 2.17 Trolox 0.1 mM -100 ± 0.0…”

Section: Antioxidant Activitymentioning

confidence: 99%

“…Further progress in the development of anticancer aminoferrocene prodrugs was systematically reviewed in 2019 [20]. N-alkylaminoferrocene-based prodrugs, activated under cancer-specific conditions, i.e., a high ROS concentration, were able to reduce the mitochondrial membrane potential, but also showed low efficacy and high toxicity [21][22][23]. Structural optimization led to aminoferrocene derivatives that are able to generate mitochondrial ROSs only in cancer cells, and therefore have anticancer activity in vivo [24].…”

Section: Introductionmentioning

confidence: 99%

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Recent Advances in the Field of Amino Acid-Conjugated Aminoferrocenes—A Personal Perspective

Čakić Semenčić,

Kovačević,

Barišić

2024

IJMS

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The development of turn-based inhibitors of protein–protein interactions has attracted considerable attention in medicinal chemistry. Our group has synthesized a series of peptides derived from an amino-functionalized ferrocene to investigate their potential to mimic protein turn structures. Detailed DFT and spectroscopic studies (IR, NMR, CD) have shown that, for peptides, the backbone chirality and bulkiness of the amino acid side chains determine the hydrogen-bond pattern, allowing tuning of the size of the preferred hydrogen-bonded ring in turn-folded structures. However, their biological potential is more dependent on their lipophilicity. In addition, our pioneering work on the chiroptical properties of aminoferrocene-containing peptides enables the correlation of their geometry with the sign of the CD signal in the absorption region of the ferrocene chromophore. These studies have opened up the possibility of using aminoferrocene and its derivatives as chirooptical probes for the determination of various chirality elements, such as the central chirality of amino acids and the helicity of peptide sequences.

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Section: Antioxidant Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Field of Amino Acid-Conjugated Aminoferrocenes—A Personal Perspective

Čakić Semenčić,

Kovačević,

Barišić

2024

IJMS

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“…Recently, Thakur et al successfully designed ferrocene–coumarin platforms as PET-based chemosensors of Fe 3+ and Cu 2+ cations [ 15 , 16 ]. In the field of anticancer metallodrugs, Mokhir et al have introduced several ROS-sensitive, ferrocene–fluorophore conjugates whose fluorescence emission is partially quenched by PET, whereas their oxidation results in an increased fluorescence emission either in vitro or in cancer cells due to PET release [ 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Electrochemical and Fluorescence Properties of the First Fluorescent Member of the Ferrocifen Family and of Its Oxidized Derivatives

et al. 2022

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The first fluorescent ferrociphenol derivative (P797) has been synthesized via McMurry cross-coupling followed by copper-catalyzed [3 + 2] azide-alkyne cycloaddition of the fluorescent group coumarin. Cyclic voltammograms of P797 exhibit either a monoelectronic oxidation wave ascribed to the ferrocene Fe(II) → Fe(III) conversion or a three-electron oxidation process in the presence of a base, leading to a Fe(III) quinone methide adduct. This general sequence is consistent with those previously described for non-fluorescent ferrociphenols. Furthermore, the fluorescence properties of P797 and its oxidized intermediates appear to strongly depend on the redox state of the ferrocene group. Indeed, electrochemical generation of Fe(III) (ferrocenium) states markedly increases the fluorescence emission intensity. In contrast, the emission of the Fe(II) (ferrocene) states is partially quenched by photoinduced electron transfer (PET) from the Fe(II) donor to the coumarin acceptor and by concentration-dependent self-quenching. Owing to its switchable fluorescence properties, complex P797 could represent an innovative and useful tool to study the biodistribution and the redox state of ferrocifens in cancer cells.

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Red Fluorescent Aminoferrocene (Pro)Drugs for in Cellulo and in Vivo Imaging

Chernii,

Selin,

Bila

et al. 2024

Chemistry A European J

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Red fluorescent dyes are usually charged, lypophilic molecules with the relatively high molecular weight, which tend to localize in specific intracellular locations, e.g., a cyanine dye Cy5 is biased towards mitochondria. They are often used as markers of biomolecules including nucleic acids and proteins. Since molecular weight of the dyes is much smaller than that of the biomolecules, the labelling has a negligible effect on the properties of the biomolecules. In contrast, conjugation of the dyes to low molecular weight (pro)drugs can dramatically alter their properties. For example, conjugates of Cy5 with lysosome‐targeting aminoferrocenes accumulate in mitochondria and exhibit no intracellular effects characteristic for the parent (pro)drugs. Herein we tested several neutral and negatively charged dyes for labelling lysosome‐targeting aminoferrocenes 7 and 8 as well as a non‐targeted control 3. We found that a BODIPY derivative BDP‐TR exhibits the desired unbiased properties: the conjugation does not disturb the intracellular localization of the (pro)drugs, their mode of action and cancer cell specificity. We used the conjugates to clarify the mechanism of action of the aminoferrocenes. In particular, we identified new intermediates, explained why lysosome targeting aminoferrocenes are more potent than their non‐targeted counterparts and evaluated their distribution in vivo.

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Aminoferrocene‐Based Anticancer Prodrugs Labelled with Cyanine Dyes for in vivo Imaging

Cited by 7 publications

References 16 publications

Recent Advances in the Field of Amino Acid-Conjugated Aminoferrocenes—A Personal Perspective

Recent Advances in the Field of Amino Acid-Conjugated Aminoferrocenes—A Personal Perspective

Synthesis, Electrochemical and Fluorescence Properties of the First Fluorescent Member of the Ferrocifen Family and of Its Oxidized Derivatives

Red Fluorescent Aminoferrocene (Pro)Drugs for in Cellulo and in Vivo Imaging

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