DNA-binding properties of ruthenium(II) complexes with the bidentate ligand 5-chloro-2-(phenylazo)pyridine

Abstract

A bidentate ligand, 5-chloro-2-(phenylazo)pyridine (Clazpy), and its two polypyridyl ruthenium(II) complexes, [Ru(Clazpy) 2 bpy]Cl 2 Á7H 2 O (1) and [Ru(Clazpy) 2 phen]Cl 2 Á8H 2 O (2), were synthesized and characterized. The DNA-binding properties of these complexes with DNA, the breast cancer susceptibility gene 1 (BRCA1), and the pBIND plasmid DNA were probed by photocleavage, electronic absorption titration, ethidium bromide quenching, and thermal denaturation. Both complexes were found to bind to the BRCA1 fragment through the intercalative mode into the base pairs of DNA, and the DNA-binding constants (K b ) for 1 and 2 were 7.0 9 10 4 M -1 and 5.1 9 10 5 M -1 , respectively. In addition, both complexes enhanced the single-stranded cleavage of the plasmid DNA. Under comparable experimental conditions, 2 cleaved DNA more effectively than 1, in a dose-response manner. The data indicated that the binding affinity of these two complexes to DNA was dependent on the aromatic planarity and hydrophobicity of the intercalative polypyridyl ligand.

Cellular responses of BRCA1-defective and triple-negative breast cancer cells and in vitro BRCA1 interactions induced by metallo-intercalator ruthenium(II) complexes containing chloro-substituted phenylazopyridine

“…Platinum drugs exert their antitumor effects by binding to DNA, thereby changing the replication of DNA and inhibiting the growth of the tumor cells. For ruthenium-based drugs, there has been some evidence demonstrating an interaction between ruthenium complexes and DNAs [ 18 , 20 , 30 ]. Our previous study has demonstrated that 1 and 2 bound to the specified DNA fragment of the human breast cancer suppressor gene 1 (BRCA1) through the intercalative mode into the base pairs of DNA, and the DNA-binding constants (K b ) for 1 and 2 were 7.09 × 10 4 M -1 and 5.19 × 10 5 M -1 , respectively.…”

“…Our previous study has demonstrated that 1 and 2 bound to the specified DNA fragment of the human breast cancer suppressor gene 1 (BRCA1) through the intercalative mode into the base pairs of DNA, and the DNA-binding constants (K b ) for 1 and 2 were 7.09 × 10 4 M -1 and 5.19 × 10 5 M -1 , respectively. This data indicated that the binding affinity of these two complexes to DNA was dependent on the aromatic planarity and hydrophobicity of the intercalative polypyridyl ligand [ 18 ]. We further investigated whether the ruthenium(II) complexes with the bidentate ligand 5-chloro-2-(phenylazo)pyridine were capable of blocking BRCA1 amplification.…”

“…Several ruthenium compounds have exhibited high cytotoxicity towards cancer cells and for inducing apoptosis [ 15 - 17 ]. In addition, extensive investigations of ruthenium-based compounds has mainly focused on the characterization of ruthenium-DNA adducts [ 12 , 18 - 20 ] and has paid less attention to other potential cellular targets. For ruthenium-based drug candidates, their precise mechanisms of action as anticancer activities remain comparatively unexplored.…”

“…Therefore, it is of interest to consider this metal-based compound as a therapeutic agent perhaps for aggressive triple-negative and BRCA1-defective breast cancers (TNBC). In the present study, we have explored the cellular responses to metallo-intercalator ruthenium(II) complexes with the Clazpy ligand, [Ru(Clazpy) 2 bpy]Cl 2 .7H 2 O ( 1 ) and [Ru(Clazpy) 2 phen]Cl 2 .8H 2 O ( 2 ) (Figure 1 ) [ 18 ], in selected BRCA1-defective and triple-negative breast cancer cells as well as by testing the possibility that the N -terminal BRCA1 RING domain protein was a potential biomolecular target for these ruthenium-based anticancer agents in breast cancers.…”

Synthesis, characterization, and biological studies of novel Ni(II) and Zn(II) complexes with 5-chloro-2-(phenylazo)pyridine

“…1). The ruthenium complexes of [Ru(Clazpy) 2 (L)]Cl 2 · xH 2 O, where L is either 2,2 -bipyridine (bpy) or 1,10-phenanthroline (phen), have been studied for their DNA-binding properties 10 . However, coordination complexes of Clazpy with other metal ions are few 11 , and to our knowledge, their antimicrobial activities have not yet been reported.…”