Metabolic Aspects of Palladium(II) Potential Anti-Cancer Drugs

Abstract

This mini-review reports on the existing knowledge of the metabolic effects of palladium [Pd(II)] complexes with potential anticancer activity, on cell lines and murine models. Most studies have addressed mononuclear Pd(II) complexes, although increasing interest has been noted in bidentate complexes, as polynuclear structures. In addition, the majority of records have reported in vitro studies on cancer cell lines, some including the impact on healthy cells, as potentially informative in relation to side effects. Generally, these studies address metabolic effects related to the mechanisms of induced cell death and antioxidant defense, often involving the measurement of gene and protein expression patterns, and evaluation of the levels of reactive oxygen species or specific metabolites, such as ATP and glutathione, in relation to mitochondrial respiration and antioxidant mechanisms. An important tendency is noted toward the use of more untargeted approaches, such as the use of omic sciences e.g. , proteomics and metabolomics. In the discussion section of this mini-review, the developments carried out so far are summarized and suggestions of possible future developments are advanced, aiming at recognizing that metabolites and metabolic pathways make up an important part of cell response and adaptation to therapeutic agents, their further study potentially contributing valuably for a more complete understanding of processes such as biotoxicity or development of drug resistance.

Synthesis, Characterization, Thermal Analysis, DFT, and Cytotoxicity of Palladium Complexes with Nitrogen-Donor Ligands

“…Pd(II) complexes are kinetically and thermodynamically stable and are 10 5 more reactive than analogues Pt(II) complexes. Nevertheless they display lower antitumor activities, probably due to their high reactivity that does not preserve the complex structure until it reach the DNA targets [13][14][15][16][17]. Pd(II) complexes based on nitrogen ligands attracted increasing attention due to their beneficial pharmacological properties [18].…”

Cytotoxic Action of Palladium-Based Compound on Prostate Stem Cells, Primary Prostate Epithelial Cells, Prostate Epithelial Cells, and Prostate Cell Lines

“…Cancer is a crucial public health issue worldwide, and additional patients are in distress because of prostate cancer. There are around 12.7 million fresh cases of cancer, which predicted 7.6 million deaths to have taken place [ 1 ]. There is a considerable number of cancer deaths that could be stopped using advanced identification and detection followed by treatments.…”

Platinum and Palladium Complexes as Promising Sources for Antitumor Treatments

“…Excessive generation of reactive oxygen species (ROS) was the result of Pd(II) reacting with thiol groups of proteins, including antioxidant system proteins (glutathione-S-transferase (GST), glutathione peroxidases (GPxs), catalase (CAT), and glutathione (GSH)), and a decrease in their levels in the cell. In addition, cell arrest in the G 2 /M phase of the cell cycle was also noted [ 37 , 38 ]. Despite the many similarities between palladium(II)-based complexes and their platinum analogs, both in terms of chemistry and mechanism of action, there are some minor differences between them.…”