How half sandwich ruthenium compounds interact with DNA while not being hydrolyzed; a comparative study

Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment

“…First of all, the signal of uncoordinated aminomethylphosphane is situated in the negative part of Nevertheless, in cellular environment there is a plethora of electron-donating species and in such conditions the substitution of any ligand cannot be excluded. Furthermore, it is wellknown that hydrolysis, that is suppressed extracellularly, due to the high chloride concentration (104 mM), it occurs inside the cell, in cytoplasm or the nucleus, where the chloride concentration is significantly lower [6]. Thus, presumably, the studied complexes will hydrolyze relatively very slowly inside tumor cells, reaching the equilibrium with an amount of the complex remaining non-hydrolyzed.…”

“…The discovery of therapeutic activity of (ImH)[trans-RuCl 4 (DMSO)Im] (NAMI-A) and (IndH)[trans-RuCl 4 (Ind) 2 ] (KP1019) resulted in greater interest in the field of ruthenium complexes possessing prospective cytotoxic activity, including organometallic ruthenium(II) compounds [1][2][3][4][5]. At present, two classes of half sandwich η 6 -arene-Ru(II) complexes are of the most interest: (i) the monofunctional compounds, represented by [(η 6 -cym)Ru(en)Cl]PF 6 (cym = 1-methyl-4-(1-methylethyl)benzene, en = 1,2-ethylenediamine) and (ii) the bifunctional, represented by [((η 6 -cym))Ru(pta)Cl 2 ] (pta = 1,3,5-triaza-7-phospha-tricyclo-[3.3.1.1]decane), termed RAPTA-C. The first complex [(η 6 -cym)Ru(en)Cl](PF 6 ) shows significant antitumor activity, comparable to that of carboplatin, towards various cancer cell lines in vitro.…”

“…The first complex [(η 6 -cym)Ru(en)Cl](PF 6 ) shows significant antitumor activity, comparable to that of carboplatin, towards various cancer cell lines in vitro. On the other hand, RAPTA-C exhibits low in vitro activity, while being active in vivo, inhibiting lung metastases in mice [6]. Furthermore, combination of two or even more multifunctional structural elements brings into play different properties of a compound and may result in improving the spectrum of biological activity, novel mechanisms of action, and modification of the pharmacokinetic profile of the drug [7,8].…”

Synthesis, DNA-Binding, Anticancer Evaluation, and Molecular Docking Studies of Bishomoleptic and Trisheteroleptic Ru-Diimine Complexes Bearing 2-(2-Pyridyl)-quinoxaline

“…Taking into account the experimental data of DNA binding for 1 and 2, molecular docking studies were performed in order to identify the most preferable binding site on the biomolecule, assuming that DNA and ruthenium complexes are rigid. Complex 1 was already studied through 1D and 2D NMR, indicating that both isomers Λ-and Δ-interact with oligonucleotides by the same mode and can provide us a good indicator for our docking calculations [21]. e selected optimized structures of complexes 1 and 2 obtained from DFT calculations in the gas phase were used in docking experiments, utilizing crystallography data.…”

“…Furthermore, incorporation of 2, 2′pq in Pt-diamine complexes [19] and study against murine leukemia results in IC 50 values in the range of ∼40 μM. Square planar and octahedral Rh(I) and Rh(II) complexes comprise 2, 2′-pq as a ligand exhibit activity against the platelet-activating factor (PAF) [20], while organometallic Ru(II) complexes with arene ligands and 2, 2′-pq [21] bind to oligonucleotides and exhibit cytotoxic properties with IC 50 < 1 μM. Ruthenium complexes bearing 2, 2′-pq ligand have also been reported [22], with both Δ-and Λ-enantiomers of [Ru(bpy) 2 (2, 2′-pq)] 2+ binding to oligonucleotide duplex d(CGCGAATTCGCG) 2 [23].…”