<i>C</i>-Glycosylation in platinum-based agents: a viable strategy to improve cytotoxicity and selectivity

Cucciolito, Maria Elena; Bossa, Ferdinando De Luca; Esposito, Roberto; Ferraro, Giarita; Iadonisi, Alfonso; Petruk, Ganna; D’Elia, Luigi; Romanetti, Claudia; Traboni, Serena; Tuzi, Angela; Monti, Daria Maria; Merlino, Antonello; Ruffo, Francesco

doi:10.1039/c8qi00664d

Cited by 20 publications

(29 citation statements)

References 64 publications

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“…The second main procedure involved oxidative addition of an electrophile X‐Y to a three‐coordinate Pt(0) precursor of formula [Pt(dmphen)(alkene)] (Scheme ). This procedure was successful also for sugar derivatives, and in the case of the addition of 1‐iodoglucosydes, chair inversion and retention of the configuration at C1 were observed, as clearly indicated by the NMR coupling constants of the sugar signals …”

Section: Synthesis and Chemical Properties Of Five‐coordinate Pt(imentioning

confidence: 77%

Five‐Coordinate Platinum(II) Compounds as Potential Anticancer Agents

et al. 2019

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Five‐coordinate platinum(II) complexes represent a minority compared to the well‐known class of square‐planar species. However, since the first appearances in the literature, their general properties have attracted much interest. In particular, their potential to act as anticancer agents has been considered, and several studies have demonstrated their effectiveness as pro‐drugs. The review traces the progress of these investigations over time and the subsequent refinements in the structures. It also reports their synthesis, general properties, cytotoxic activity and ability to interact with biological macromolecules.

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Section: Synthesis and Chemical Properties Of Five‐coordinate Pt(imentioning

confidence: 77%

Five‐Coordinate Platinum(II) Compounds as Potential Anticancer Agents

et al. 2019

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“…To overcome these side effects, structurally and functionally unique metallodrugs have been designed [1]. These include trans -configured complexes [13], Pt(IV) compounds [14,15], polynuclear complexes [16], photoactivatable complexes [17], and even five-coordinate (trigonal bi-pyramidal) complexes of general formula [Pt(X)(Y)(N–N)(olefin)] (X = halide; Y = alkyl, aryl, or halide) [18,19]. Five-coordinate Pt(II) species are usually stabilized by the presence of sterically hindered nitrogen chelates, e.g., 2,9-Me 2 -1,10-phenanthroline (dmphen, Me = methyl).…”

Section: Introductionmentioning

confidence: 99%

“…Five-coordinate (5C) Pt(II) complexes possess a good thermal stability, can be stored at air for a long time, and show interesting antitumor properties in vitro [18,19,23,24]. However, very little is known about the mechanism of action of these compounds, and even less is known about the reactivity with biological macromolecules, like nucleic acids and proteins.…”

Section: Introductionmentioning

confidence: 99%

Reaction with Proteins of a Five-Coordinate Platinum(II) Compound

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Cucciolito

et al. 2019

IJMS

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Stable five-coordinate Pt(II) complexes have been highlighted as a promising and original platform for the development of new cytotoxic drugs. Their interaction with proteins has been scarcely studied. Here, the reactivity of the five-coordinate Pt(II) compound [Pt(I)(Me) (dmphen)(olefin)] (Me = methyl, dmphen = 2,9-dimethyl-1,10-phenanthroline, olefin = dimethylfumarate) with the model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease (RNase A) has been investigated by X-ray crystallography and electrospray ionization mass spectrometry. The X-ray structures of the adducts of RNase A and HEWL with [Pt(I)(Me)(dmphen)(olefin)] are not of very high quality, but overall data indicate that, upon reaction with RNase A, the compound coordinates the side chain of His105 upon releasing the iodide ligand, but retains the pentacoordination. On the contrary, upon reaction with HEWL, the trigonal bi-pyramidal Pt geometry is lost, the iodide and the olefin ligands are released, and the metal center coordinates the side chain of His15 probably adopting a nearly square-planar geometry. This work underlines the importance of the combined use of crystallographic and mass spectrometry techniques to characterize, in detail, the protein–metallodrug recognition process. Our findings also suggest that five-coordinate Pt(II) complexes can act either retaining their uncommon structure or functioning as prodrugs, i.e., releasing square-planar platinum complexes as bioactive species.

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“…Anyway, the remarkable cytotoxicity observed for these compounds towards a wide range of tumor cell lines, was accompanied by a poor selectivity, similarly to cisplatin alone. A good solution was to synthesize compounds in which the glycoconjugation is realized through a direct link between platinum and a carbon atom of the carbohydrate residue (Figure 23), in order to avoid the loss of the sugar portion before the internalization [80] …”

Section: Metal Complexes As Cancer Therapeutic Agentsmentioning

confidence: 99%

Glycoconjugated Metal Complexes as Cancer Diagnostic and Therapeutic Agents

et al. 2020

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The possibility of selectively delivering metal complexes to a defined cohort of cells on the basis of their metabolic features is a highly challenging goal, which may be extremely useful for a series of purposes, including diagnosis and therapy of pathological states, such as cancer. Tumor cells display augmented requests for carbohydrates and, in particular, for glucose in order to sustain their high proliferation rate, which causes an increased glycolytic process (Warburg effect). Since several metal complexes display diagnostic and/or therapeutic properties, their conjugation to carbohydrate portions often induce their preferential accumulation in cancer cells, similarly to what is observed with fluorodeoxyglucose (FDG). In this review we have considered the latest developments of glycoconjugates containing metal complexes in their structures. These compounds are classified as diagnostic or therapeutic agents and are further systematically discussed on the basis of the metal atom they contain. Several diagnostic techniques are possible with these probes, since, depending on the metal species included in their structures, they may be employed in nuclear medicine (PET, SPECT), magnetic resonance imaging, luminescence and phosphorescence. At the same time, the lack of selective cytotoxicity displayed by several metal‐based chemotherapeutic agents, may also be solved by the conjugation of these agents to carbohydrate portions. Overall, data so far available reveal the great potential of this chemical class in the early detection and in the cure of severe neoplastic diseases, which still needs to be fully explored in the clinic.

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C-Glycosylation in platinum-based agents: a viable strategy to improve cytotoxicity and selectivity

Abstract: The glycosylation of five-coordinate Pt(ii) compounds through a Pt–C linkage can be a very effective strategy for attacking cancer cells, while preserving the survival of the healthy ones.

Cited by 20 publications

References 64 publications

Five‐Coordinate Platinum(II) Compounds as Potential Anticancer Agents

Five‐Coordinate Platinum(II) Compounds as Potential Anticancer Agents

Reaction with Proteins of a Five-Coordinate Platinum(II) Compound

Glycoconjugated Metal Complexes as Cancer Diagnostic and Therapeutic Agents

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