DNA binding properties, histidine interaction and cytotoxicity studies of water soluble ruthenium(ii) terpyridine complexes

Abstract

In this study, two representatives of previously synthesized ruthenium(II) terpyridine complexes, i.e., and P2 against all the selected cell lines. The results on in vitro anticancer activity confirmed that only compounds that hydrolyze the monodentate ligand at a reasonable rate show moderate activity, provided that the chelate ligand is a hydrogen bond donor.

New 4′-(4-chlorophenyl)-2,2′:6′,2″-terpyridine ruthenium(II) complexes: Synthesis, characterization, interaction with DNA/BSA and cytotoxicity studies

“…It can be seen that both complexes hydrolyze at a similar rate, k obs = 6.10 × 10 -3 s - hydrolysis, to DNA through guanine N7 [37]. In our previous work, we revealed that the Ru(II)-tpy complexes 4 -6 both intercalate and covalently bind to CT DNA [7]. The combination of these modes of interaction can be utilized to improve the binding affinity and selectivity of ruthenium complexes.…”

“…within minutes) and they are capable to act as hydrogen bond donors through the chelating ligand. These two features seem to be a prerequisite for antiproliferative activity [7,8].…”

“…Recently, we developed a series of new polypyridyl complexes of the general formula mer-[Ru(L 3 )(N-N)(X)][Y]n where L 3 is either tpy (2,2':6',2''-terpyridine) or Cl-tpy (4'-chloro-2,2':6',2''-terpyridine), N-N is a bidentate chelating ligand (1,2-diaminoethane (en), 1,2diaminocyclohexane (dach), 2,2'-bipyridine (bpy)), X is a monodentate ligand (Cl or dmso-S), Y is the counter anion (Cl, PF 6 or CF 3 SO 3 ), and n depends on the nature of chel and X [6,7]. It was evidenced that ruthenium complexes strongly bind DNA by a dual function: by intercalation, interacting with the DNA helix through the insertion of the planar terpyridine ring between the DNA base pairs, and by covalent binding to guanine N7 [7]. In addition, it was proved that these complexes can covalently bind to bovine serum albumin (BSA) through the imidazole ring of histidine [8].…”

“…The cytotoxicity of these Ru(II)-tpy complexes was studied by MTT assay using human lung carcinoma (A549), human colon carcinoma (HCT116) and mouse colon carcinoma (CT26) cell lines. It was found that only [Ru(Cltpy)(en)Cl]Cl and [Ru(Cl-tpy)(dach)Cl]Cl showed from high to moderate in vitro cytotoxicity, with IC 50 's of 32.80 ─ 66.30 µM and 72.80 ─ 110.80 µM, respectively [7]. It is worth noting that both Ru(II)-tpy complexes hydrolyze the chloride ligand at a reasonable rate (i.e.…”

Complex formation between [(η6-p-cym)Ru(H2O)3]2+ and oligopeptides containing three histidyl moieties

“…It is widely accepted that these proteins have determining role in the uptake of platinum compounds therefore these interactions will determine the overall drug distribution and excretion and differences in efficacy, activity and toxicity [2]. Studies, therefore, involving the binding of imidazole, histidine or histidyl side chains to various metal ions are in the focus of intensive research [3][4][5][6][7][8][9].…”