Lipophilicity-antiproliferative activity relationship study leads to the preparation of a ruthenium(II) arene complex with considerable in vitro cytotoxicity against cancer cells and a lower in vivo toxicity in zebrafish embryos than clinically approved cis-platin

Study of the cytotoxic and genotoxic potential of the carbonyl ruthenium(II) compound, ct‐[RuCl(CO)(dppb)(bipy)]PF6 [dppb = 1,4‐bis(diphenylphosphino)butane and bipy = 2,2′‐bipyridine], by in vitro and in vivo assays

“…These erythrocytes have a relatively short lifespan so that any micronucleus is the result of recently induced chromosome damage (Hayashi et al, ). Taken together, the results suggest that the compound studied does not induce genotoxicity in healthy tissues and that its mechanism of action differs from that of cisplatin, confirming the lower toxic effects of ruthenium compounds compared to cisplatin reported in the literature (Haghdoost et al, ; Van Rijt & Sadler, ; Wang et al, ).The in vivo comet assay has the advantage that it allows the identification of possible DNA damage in different organs of the animal, and that it is sensitive to the detection of low degrees of DNA damage (Hayashi et al, ). The comet assay for the detection of genotoxic effects is usually performed in the liver, which is the main organ for the metabolic activation of substances after systemic exposure (Rothfuss et al, ).…”

“…confirming the lower toxic effects of ruthenium compounds compared to cisplatin reported in the literature(Haghdoost et al, 2017;Van Rijt & Sadler, 2009;Wang et al, 2015).The in vivo comet assay has the advantage that it allows the identification of possible DNA damage DNA damage detected by the comet assay in animals treated with ct-[RuCl(CO)(dppb)(bipy)]PF 6 and the respective control groups. A, Percentage of DNA in the tail (% DNA).…”

“…Within this context, the key factors for the development of active metal compounds are the control of toxicity and side effects and targeting the metal to specific tissues, organs or cells where activity is required (Novak et al, 2016;Ronconi & Sadler, 2007). For this reason, researchers choose organic ligands to increase selectivity for specific tissues and to minimize side effects, with both the metal and the ligands playing an important role in the recognition of target sites (Haghdoost, Golbaghi, Létourneau, Patten, & Castonguay, 2017;Storr, Thompson, & Orvig, 2006;Tfouni et al, 2012;Van Rijt & Sadler, 2009). Ruthenium(II) and (III) compounds with different biological ligands have attracted attention in recent years because of their better antitumor activity compared to cisplatin, such as NAMI-A ([ImH]{trans-[RuCl 4 (Im)(DMSO)], Im = imidazole) and KP1019 ([IndH]{trans-[RuCl 4 (Ind) 2 ]}, Ind = indazole), which are in clinical trials, and ruthenium(II) polypyridyl complexes.…”

“…Ruthenium(II) and (III) compounds with different biological ligands have attracted attention in recent years because of their better antitumor activity compared to cisplatin, such as NAMI-A ([ImH]{trans-[RuCl 4 (Im)(DMSO)], Im = imidazole) and KP1019 ([IndH]{trans-[RuCl 4 (Ind) 2 ]}, Ind = indazole), which are in clinical trials, and ruthenium(II) polypyridyl complexes. These compounds have shown low toxicity in healthy tissues in in vitro and in vivo assays (Grozav et al, 2015;Haghdoost et al, 2017;Van Rijt & Sadler, 2009;Wang et al, 2014;Wang, Zhang, Ji, & Chao, 2015). Other anticancer activities include the interaction with proteins, induction of apoptosis, inhibition of metastasis, inhibition of topoisomerase, interaction with DNA and antiangiogenic effects (Bergamo, Masi, Dyson, & Sava, 2008;Du et al, 2011;Li, Wong, Chen, & Zheng, 2012;Martínez, Suárez, Shand, Magliozzo, & Sánchez-Delgado, 2011;Moreno et al, 2011;Nazarov et al, 2013;Sava et al, 2003).…”

Synthesis, spectroscopic characterization, thermal behaviour, in vitro antimicrobial and anticancer activities of novel ruthenium tricarbonyl complexes containing monodentate V‐shaped Schiff bases

“…In the field of synthetic chemistry of transition metals, ruthenium is well developed and has attracted much attention as a building block for innovative new metalloid pharmaceuticals due to its low general toxicity, which contrasts with the pharmacological properties of platinum drugs. This low toxicity has been ascribed to selective uptake of ruthenium compounds by cancer cells mediated via the transferrin cycle and to mechanisms such as activation through reduction …”