Excessive cellular oxidative stress is widely perceived as a key factor in pathophysiological conditions and cancer development. Healthy cells use several mechanisms to maintain intracellular levels of reactive oxygen species (ROS) and overall redox homeostasis to avoid damage to DNA, proteins, and lipids. Cancer cells, in contrast, exhibit elevated ROS levels and upregulated protective antioxidant pathways. Counterintuitively, such elevated oxidative stress and enhanced antioxidant defence mechanisms in cancer cells provide a therapeutic opportunity for the development of drugs with different anticancer mechanisms of action (MoA). In this review, oxidative stress and the role of ROS in cells are described. The tumoursuppressive and tumour-promotive functions of ROS are discussed, and these two different therapeutic strategies (increasing or decreasing ROS to fight cancer) are compared. Clinically approved drugs with demonstrated oxidative stress anticancer MoAs are highlighted followed by description of examples of metal-based anticancer drug candidates causing oxidative stress in cancer cells via novel MoAs.

Highlights A new family of indole-containing arene ruthenium organometallic compounds are active against several bacterial species and drug resistant strains Bactericidal activity observed against various Gram negative, Gram positive and acid-fast bacteria, demonstrating broad-spectrum inhibitory activity Compound series exhibits low toxicity against human cells Shows considerable promise as next generation antibiotics

Schizophrenia is a complex and unpredictable mental disorder which affects several domains of cognition and behaviour. It is a heterogeneous illness characterised by positive, negative, and cognitive symptoms, often accompanied by signs of depression. In this tutorial review, we discuss recent progress in understanding the target sites and mechanisms of action of second-generation antipsychotic drugs. Progress in identifying and defining target sites has been accelerated recently by advances in neuroscience, and newly developed agents that regulate signalling by the main excitatory neurotransmitters in the brain are surveyed. Examples of novel molecules for the treatment of schizophrenia in preclinical and clinical development and their industrial sponsors are highlighted.

Ruthenium compounds have been shown to be promising alternatives to platinum(II) drugs. However, their clinical success depends on achieving mechanisms of action that overcome Pt‐resistance mechanisms. Electron‐deficient organoruthenium complexes are an understudied class of compounds that exhibit unusual reactivity in solution and might offer novel anticancer mechanisms of action. Here, we evaluate the in vitro and in vivo anticancer properties of the electron‐deficient organoruthenium complex [(p‐cymene)Ru(maleonitriledithiolate)]. This compound is found to be highly cytotoxic: 5 to 60 times more potent than cisplatin towards ovarian (A2780 and A2780cisR), colon (HCT116 p53+/+ and HCT116 p53−/−), and non‐small cell lung H460 cancer cell lines. It shows no cross‐resistance and is equally cytotoxic to both A2780 and A2780cisR cell lines. Furthermore, unlike cisplatin, the remarkable in vitro antiproliferative activity of this compound appears to be p53‐independent. In vivo evaluation in the hollow‐fibre assay across a panel of cancer cell types and subcutaneous H460 non‐small cell lung cancer xenograft model hints at the activity of the complex. Although the impressive in vitro data are not fully corroborated by the in vivo follow‐up, this work is the first preclinical study of electron‐deficient half‐sandwich complexes and highlights their promise as anticancer drug candidates.

The synthesis, characterisation and evaluation of the in vitro cytotoxicity of four indole-based half-sandwich metal complexes towards two ovarian cancer cell lines (A2780 and A2780cisR) and one normal prostate cell line (PNT2) are presented herein. Although capable of inducing catalytic oxidation of NADH and able to reduce NAD+ with high turnover frequencies, in cells and in the presence of sodium formate, these complexes also strongly interact with biomolecules such as glutathione. This work highlights that efficient out-of-cells catalytic activity might lead to higher reactivity towards biomolecules, thus inhibiting the in-cells catalytic processes.

An evaluation of the in vitro cytotoxicity of nine electron‐deficient half‐sandwich metal complexes towards two colorectal cancer cell lines (HCT116 p53+/+, HCT116 p53−/−) and one normal prostate cell line (PNT2) is presented herein. Three complexes were found to be equally cytotoxic towards both colorectal cancer cell lines, suggesting a p53‐independent mechanism of action. These complexes are 12 to 34× more potent than cisplatin against HCT116 p53+/+ and HCT116 p53−/− cells. Furthermore, they were found to exhibit little or no cytotoxicity towards PNT2 normal cells, with selectivity ratios greater than 50. To gain an insight into the potential mechanisms of action of the most active compounds, their effects on the expression levels of a panel of genes were measured using qRT‐PCR against treated HCT116 p53+/+ and HCT116 p53−/− cells, and cell‐cycle analysis was carried out.

The synthesis, characterisation, and evaluation of the in vitro cytotoxicity of five maleonitriledithiolate‐based ruthenium metal complexes bearing various phosphine ligands towards two ovarian cancer cell lines (A2780 and A2780cisR), one non‐small‐cell lung cancer cell line (H460) and one normal prostate cell line (PNT2) are presented herein. These 18‐electron complexes were designed with four water‐soluble phosphine ligands to increase the water‐solubility character of the corresponding electron‐deficient ruthenium complex which showed great in vitro promises, and triphenylphosphine for comparison. The complexes with triphenylphosphine‐3,3′,3′′‐trisulfonic acid and triphenylphosphine present similar cytotoxicity compared to the 16‐electron precursor, with equal cytotoxicity to both A2780 and A2780cisR. Hints at the mechanism of action suggest an apoptotic pathway based on reactive oxygen species (ROS) production. No toxicity was observed in preliminary in vivo pilot studies for these two complexes in subcutaneous A2780 and A2780cisR xenograft models, with some evidence of tumour growth delay.

Electron‐deficient half‐sandwich complexes are a class of under‐studied organometallics with demonstrated potential as metallodrug candidates. This study investigates the effect of two 16‐electron organoruthenium complexes ([(p‐cym)Ru(benzene‐1,2‐dithiolato)] (1) and [(p‐cym)Ru(maleonitriledithiolate)] (2)) on the cell viability of non‐immortalised human lymphocytes from healthy individuals. The genotoxic effects of 1 and 2 in lymphocytes are also investigated by using the Comet and cytokinesis‐block micronucleus assays. Gene expression studies were carried out on a panel of genes involved in apoptosis and the DNA damage‐repair response. Results show that the two 16‐electron complexes do not have significant effect on the cell viability of human lymphocytes from healthy individuals. However, an increase in DNA damage is induced by both compounds, presumably through oxidative stress production.