A critical review of palladium organometallic anticancer agents

Scattolin, Thomas; Voloshkin, Vladislav A.; Visentin, Fabiano; Nolan, Steven P.

doi:10.1016/j.xcrp.2021.100446

Cited by 77 publications

(62 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Molecular characteristics of the Pd(II)-based agent significantly influence drug–DNA interactions, with aromatic planar moieties as the most common ligands to promote DNA damage [ 182 ]. However, a number of different classes of ligands was used to synthesize Pd-based complexes to be tested in vitro for preliminary evaluations [ 187 ]. Another proposed target for Pd(II)-based complexes is mitochondria, resulting in the activation of both intrinsic and extrinsic apoptosis cell death pathways.…”

Section: Palladiummentioning

confidence: 99%

“…Another proposed target for Pd(II)-based complexes is mitochondria, resulting in the activation of both intrinsic and extrinsic apoptosis cell death pathways. The onset of intrinsic apoptosis is often associated with an inversion of a Bax/Bcl-2 ratio, the release of cytochrome c , and subsequently, caspase cascade activation, whereas extrinsic apoptosis activation is triggered by an increase in the expression of cell death receptor genes DR4 and DR5 [ 183 , 185 , 187 , 188 ]. It has been also demonstrated that some Pd(II)-based complexes can block the cell cycle at the G2/M phase, and other Pd(II) complexes can interact with intracellular sulfhydryl proteins’ groups, such as those of the antioxidant systems.…”

Section: Palladiummentioning

confidence: 99%

See 1 more Smart Citation

Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

et al. 2022

View full text Add to dashboard Cite

Countless expectations converge in the multidisciplinary endeavour for the search and development of effective and safe drugs in fighting cancer. Although they still embody a minority of the pharmacological agents currently in clinical use, metal-based complexes have great yet unexplored potential, which probably hides forthcoming anticancer drugs. Following the historical success of cisplatin and congeners, but also taking advantage of conventional chemotherapy limitations that emerged with applications in the clinic, the design and development of non-platinum metal-based chemotherapeutics, either as drugs or prodrugs, represents a rapidly evolving field wherein candidate compounds can be fine-tuned to access interactions with druggable biological targets. Moving in this direction, over the last few decades platinum family metals, e.g., ruthenium and palladium, have been largely proposed. Indeed, transition metals and molecular platforms where they originate are endowed with unique chemical and biological features based on, but not limited to, redox activity and coordination geometries, as well as ligand selection (including their inherent reactivity and bioactivity). Herein, current applications and progress in metal-based chemoth are reviewed. Converging on the recent literature, new attractive chemotherapeutics based on transition metals other than platinum—and their bioactivity and mechanisms of action—are examined and discussed. A special focus is committed to anticancer agents based on ruthenium, palladium, rhodium, and iridium, but also to gold derivatives, for which more experimental data are nowadays available. Next to platinum-based agents, ruthenium-based candidate drugs were the first to reach the stage of clinical evaluation in humans, opening new scenarios for the development of alternative chemotherapeutic options to treat cancer.

show abstract

Section: Palladiummentioning

confidence: 99%

Section: Palladiummentioning

confidence: 99%

Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Since about 2000, there was growing interest in organometallic palladium compounds as potential alternative anti-cancer drugs. It is mainly their good antiproliferative, high-in vitro and ex vivo anti-cancer activity, exhibited by some palladium complexes, even toward tumors resistant to cisplatin and its derivatives, combined with different modes of action compared to Pt compounds, that are the main reasons for the increasing popularity of palladium compounds as therapeutic agents, and are the key to their growing success [ 131 ]. This motivated Niehoff et al to incubate tumor spheroids with the Pd-tagged photosensitizer embedded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and investigate the efficiency of nanoparticle-based drug delivery [ 132 ].…”

Section: Single Cell Icp-ms (Sc-icp-ms)mentioning

confidence: 99%

Review about Powerful Combinations of Advanced and Hyphenated Sample Introduction Techniques with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for Elucidating Trace Element Species in Pathologic Conditions on a Molecular Level

Michalke

2022

IJMS

View full text Add to dashboard Cite

Element analysis in clinical or biological samples is important due to the essential role in clinical diagnostics, drug development, and drug-effect monitoring. Particularly, the specific forms of element binding, actual redox state, or their spatial distribution in tissue or in single cells are of interest in medical research. This review summarized exciting combinations of sophisticated sample delivery systems hyphenated to inductively coupled plasma-mass spectrometry (ICP-MS), enabling a broadening of information beyond the well-established outstanding detection capability. Deeper insights into pathological disease processes or intracellular distribution of active substances were provided, enabling a better understanding of biological processes and their dynamics. Examples were presented from spatial elemental mapping in tissue, cells, or spheroids, also considering elemental tagging. The use of natural or artificial tags for drug monitoring was shown. In the context of oxidative stress and ferroptosis iron, redox speciation gained importance. Quantification methods for Fe2+, Fe3+, and ferritin-bound iron were introduced. In Wilson’s disease, free and exchangeable copper play decisive roles; the respective paragraph provided information about hyphenated Cu speciation techniques, which provide their fast and reliable quantification. Finally, single cell ICP-MS provides highly valuable information on cell-to-cell variance, insights into uptake of metal-containing drugs, and their accumulation and release on the single-cell level.

show abstract

“…In particular, PKC ι appears to be involved in the development of resistance to cisplatin in glioblastoma cells due to suppression of GMFβ‐mediated enhancement of p38 MAP kinase signalling [6] . Against the common assumption that platinum(II) complexes show higher activity than their palladium(II) congeners due to slower ligand exchange kinetics, [7] significant anticancer potential has recently been demonstrated for various classes of palladium compounds [8] . In particular, in an interesting series of N ‐heterocyclic carbene (NHC) complexes derived from purine nucleobases, differential activity of isostructural and isoelectronic Pd(II) and Pt(II) compounds on U251 glioblastoma cells was observed [9] .…”

Section: Introductionmentioning

confidence: 99%

Structure‐activity relations of Pd(II) and Pt(II) thiosemicarbazone complexes on different human glioblastoma cell lines

Schulz¹,

Mawamba²,

Löhr³

et al. 2022

Zeitschrift anorg allge chemie

View full text Add to dashboard Cite

Ten thiosemicarbazone ligands obtained by condensation of pyridine-2-carbaldehyde, quinoline-2-carbaldehyde, 2-acetylpyridine, 2-acetylquinoline, or corresponding 2-pyridyl ketones with thiosemicarbazides RNHC(S)NHNH 2 and R=CH 3 , C 6 H 5 were prepared in good yield. The reaction of [PdCl 2 (cod)] with cod = 1,5-cyclooctadiene or K 2 [PtCl 4 ] resulted in a total of 17 Pd(II) and Pt(II) complexes isolated in excellent purity, as demonstrated by 1 H, 13 C, and, where applicable, 195 Pt NMR spectroscopy combined with CHNS analysis. The cytotoxicity of the title compounds was studied on four human glioblastoma cell lines (GaMG, U87, U138, and U343). The most active compound, with a Pd(II) metal centre, a 2-quinolinyl ring, and methyl groups on both the proximal C and distal N atoms exhibited an EC 50 value of 2.1 μM on the GaMG cell lines, thus being slightly more active than cisplatin (EC 50 3.4 μM) and significantly more potent than temozolomide (EC 50 67.1 μM). Surprisingly, the EC 50 values were inversely correlated with the lipophilicity, as determined with the "shake-flask method", and decreased with the length of the alkyl substituents (C 1 > C 8 > C 10 ). Correlation with the different structural motifs showed that for the most promising anticancer activity, a maximum of two aromatic rings (either quinolinyl or pyridyl plus phenyl) combined with one methyl group are favoured and the Pd(II) complexes are slightly more potent than their Pt(II) analogues.

show abstract

A critical review of palladium organometallic anticancer agents

Cited by 77 publications

References 103 publications

Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

Review about Powerful Combinations of Advanced and Hyphenated Sample Introduction Techniques with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for Elucidating Trace Element Species in Pathologic Conditions on a Molecular Level

Structure‐activity relations of Pd(II) and Pt(II) thiosemicarbazone complexes on different human glioblastoma cell lines

Contact Info

Product

Resources

About