Cytotoxicity of piano‐stool ruthenium cyclopentadienyl complexes bearing different imidato ligands

Abstract

AbstractIn these studies, we investigated a cytotoxic and genotoxic potential of four ruthenium cyclopentadienyl complexes bearing different imidato ligands: (η5‐cyclopentadienyl)Ru (CO)2(η1‐N‐maleimidato) (1), (η5‐cyclopentadienyl)Ru (CO)2‐N‐methoxysuccinimidato (2), (η5‐cyclopentadienyl)Ru (CO)2‐N‐ethoxysuccinimidato (3), and (η5‐cyclopentadienyl)Ru (CO)2‐N‐phthalimidato (4). We used two types of cells—normal peripheral blood mononuclear cells (PBMCs) and leukemic HL‐60 cells. We observed that complex 1 was highly cytotoxic and genotoxic, both for normal and cancer cells at concentrations from 0.5 to 250 μM. Interestingly, complex 1 was 10 times more cytotoxic to HL‐60 cells compared with PBMCs. Complexes 2–4 were cytotoxic only for HL‐60 cells at the highest used concentrations. Furthermore, we observed an increase in the viability of PBMCs after incubation with succinimide complexes 2 and 3. We also showed that complex 1 arrested cell cycle in the sub‐G1 phase and induced apoptosis. We found that different properties of studied ruthenium complexes depend significantly on the type of imide ligand bind to the ruthenium atom. The density functional theory (DFT) calculation of maleimide and succinimide revealed some significant differences of these compounds that would be related to biological activity. Our results indicate that ruthenium complex 1 should be further investigated in detail for its anticancer properties.