Anticancer organorhodium and -iridium complexes with low toxicity in vivo but high potency in vitro: DNA damage, reactive oxygen species formation, and haemolytic activity

Abstract

Dinuclear RhIII(Cp*) and IrIII(Cp*) complexes demonstrated potent in vitro anticancer activity while exhibiting low toxicity in haemolysis studies and in vivo zebrafish models.

Ligand-centred redox activation of inert organoiridium anticancer catalysts

“…Thus activation of the iodido iridium complexes is likely to involve novel pathways, distinct from chlorido complexes, and have targets other than coenzyme NADH 6 or DNA. 52 Enhanced antiproliferative activity of zwitterionic complexes…”

A Multitargeted Approach: Organorhodium Anticancer Agent Based on Vorinostat as a Potent Histone Deacetylase Inhibitor

“…When the concentration was increased to 200 mm, 4cshowed about 10 %hemolytic activity, which was asignificantly lower toxicity than, for example,that found for cisplatin, which displays 100 %hemolytic activity at this concentration, whereas ab imetallic organorhodium complex has also shown low hemolytic activity. [24] Thep rognosis for patients with solid tumors is known to be angiogenesis-dependent. [25] HDACs, among many cellular functions,a re closely linked to tumor angiogenesis,i n particular under hypoxic environment.…”

Homo‐ and Hetero‐dinuclear Arene‐Linked Osmium(II) and Ruthenium(II) Organometallics: Probing the Impact of Metal Variation on Reactivity and Biological Activity

“…Recently,a nalogous series of Rh III -Rh III and Ir III -Ir III complexes have yieldedh ighlyc ytotoxic examples able to generate reactiveo xygen species and cause appreciable DNA damage at low concentrations. [26] Au I -Au I and half-sandwichR u II -Ru II complexes have also been reported where phosphine ligands joined via ap oly(ethylene glycol) chain acted as the linking moiety.T he majority of these dinuclearc omplexes were found to be more active than mononuclear analogues against human cancer cell lines. The antiproliferative activities of the Ru II -Ru II complexes were found to be dependent on lipophilicity,w hereas antiproliferative activity for the Au I -Au I series of complexes was found not to correlate to lipophilicity.…”

“…Lipophilicity was shown to be correlated to antiproliferative activity, and the complexes were shown to be able not only to crosslink two DNA duplexes, but also form DNA–protein crosslinks. Recently, analogous series of Rh III –Rh III and Ir III –Ir III complexes have yielded highly cytotoxic examples able to generate reactive oxygen species and cause appreciable DNA damage at low concentrations …”