Evaluation of the Toxicity of Two Electron‐Deficient Half‐Sandwich Complexes against Human Lymphocytes from Healthy Individuals

Abstract

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.

Anticancer Activity of Half-Sandwich Ru, Rh and Ir Complexes with Chrysin Derived Ligands: Strong Effect of the Side Chain in the Ligand and Influence of the Metal

“…Since cytotoxicity is often related to ROS generation in Ru(II) [40,132,133] and Ir(III) [133,134] half-sandwich complexes, the ability of HL4 and its metal complexes to induce ROS generation in lung adenocarcinoma (A549) cells was studied by flow cytometry (FC) using H 2 DCFDA (dihydrodichlorofluorescein diacetate) as a probe for hydrogen peroxide, nitric oxide and peroxynitrite among other ROS [135]. More deeply, the oxidation of non-fluorescent H 2 DCFDA to highly fluorescent DCF (2 ,7diclorofluorescein) by ROS produced inside the cells is monitored by FC.…”

Anticancer Water‐Soluble Organoruthenium Complexes: Synthesis and Preclinical Evaluation

“…The absence of toxicity of 1 and 3 was confirmed against non‐immortalised lymphocytes taken from the blood of healthy individuals [12] . Primary human cells freshly isolated ex‐vivo / in‐vitro are a recognised surrogate model to examine responses in humans, owing to their intact metabolic system.…”

“…The absence of toxicity of 1 and 3 was confirmed against non-immortalised lymphocytes taken from the blood of healthy individuals. [12] Primary human cells freshly isolated ex-vivo/invitro are a recognised surrogate model to examine responses in humans, owing to their intact metabolic system. This study also confirmed that the compounds do not induce DNA damage in healthy cells at concentrations @ IC 50 values against cancer cells.…”