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

Abstract

In 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.

Piano-stool ruthenium(ii) complexes with maleimide and phosphine or phosphite ligands: synthesis and activity against normal and cancer cells

“…The complex 1 which we studied previously 34 was the most cytotoxic ruthenium complex among those currently under investigation for HL-60 cells. The IC 50 for this complex was 6.39 μM.…”

“…This molecular conformation is similar to known structures for previously determined ruthenium complexes. 34…”

“…Complex 1 was synthesized following previously published method, by photochemical reaction of CpRu(CO) 2 I with maleimide in the presence of diisopropyl amine in toluene. 34…”

“…Recently, we have found that cyclopentadienyl ruthenium complex bearing maleimidato ligand CpRu(CO) 2 (η 1 - N -maleimidato) ( 1 ) is highly cytotoxic and genotoxic, both for normal and cancer cells at the concentrations from 0.5 to 250 μM. 34…”

“…33 Recently, we have found that cyclopentadienyl ruthenium complex bearing maleimidato ligand CpRu(CO) 2 (η 1 -N-maleimidato) (1) is highly cytotoxic and genotoxic, both for normal and cancer cells at the concentrations from 0.5 to 250 µM. 34 Herein, we introduce five novel ruthenium cyclopentadienyl complexes bearing maleimide and different phosphine/phosphite ligands (2a, 2b, 3a, 3b and 3c) (Fig. 1), derivatized from complex 1 in UV-vis light induced CO ligand exchange process.…”