The Significant Influence of a Second Metal on the Antiproliferative Properties of the Complex [Ru(η⁶−C₁₀H₁₄)(Cl₂)(dmoPTA)]

Abstract

Complexes [Ru(η6−C10H14)(Cl2)(HdmoPTA)](OSO2CF3) (1), [Ru(η6−C10H14)(Cl2)(dmoPTA)] (2) and [Ru(η6−C10H14)(Cl2)‐μ‐dmoPTA‐1κP:2κ2N,N’‐MCl2] (M=Zn (3), Co (4), Ni (5), dmoPTA=3,7‐dimethyl‐1,3,7‐triaza‐5‐phosphabicyclo[3.3.1]nonane) have been synthesized and characterized by elemental analysis and spectroscopic techniques. The crystal structures of 1, 3 and 5 were obtained by single‐crystal X‐ray diffraction. The antiproliferative activity of the complexes was evaluated against colon cancer cell line Caco‐2/TC7 by using the MTT protocol. The monometallic ruthenium complexes 1 and 2 were found to be inactive, but the bimetallic complexes 3, 4 and 5 display an increased activity (IC50 3: 9.07±0.27, 4: 5.40±0.19, 5: 7.15±0.30 μM) compared to cisplatin (IC50=45.6±8.08 μM). Importantly, no reduction in normal cell viability was observed in the presence of the complexes. Experiments targeted to obtain information on the possible action mechanism of the complexes, such as cell cycle, ROS and gene expression studies, were performed. The results showed that the complexes display different properties and action mechanism depending on the nature of metal, M, bonded to the CH3NdmoPTA atoms.

Evaluation of the Antiproliferative Properties of CpRu Complexes Containing N-Methylated Triazaphosphaadamantane Derivatives

“…In this line, complexes containing 3,7-dimethyl-1,3,7-triaza-5phosphabicyclo[3.3.1]nonane (dmoPTA), which is a hydrolysis product of N,N′-dimethyl-1,3,5-triaza-7-phosphaadamantane (dmPTA) (3, Figure 1), display a very good antiproliferative profle [23], surpassing the activity of cisplatin up to 200 times in some cases [24]. Some of the most active examples of this family of compounds are heterometallic complexes in which the dmoPTA ligand is binding ruthenium by the phosphorus atom and chelates harder metals through methylated nitrogens [24][25][26][27][28][29], and have been studied along with other complexes presented in this work together with the free ligands by 15 N NMR. [30].…”

Impact of denticity of chromone/chromene thiosemicarbazones in the ruthenium(II)‐DMSO complexes on their cytotoxicity against breast cancer cells

“…DMSO can diffuse readily through biological membrane and improve the diffusion of coordinated metal ion. [ 9 ] The importance of DMSO ligand was highlighted by comparing the chemical effect of DMSO in NAMI with imidazole ligand in similarly structured ImH[ trans ‐RuCl 4 (Im) 2 ] (KP418). The π‐acceptor property of S ‐coordinated DMSO caused a decrease in the reduction potential of Ru(III) → Ru(II).…”