Antiproliferative activity of ruthenium(ii) arene complexes with mono- and bidentate pyridine-based ligands

Abstract

A series of Ru(II) arene complexes of mono- and bidentate N-donor ligands with carboxyl or ester groups and chlorido ancillary ligands were synthesised and structurally characterised. The complexes have a distorted tetrahedral piano-stool geometry. The binding interaction was studied with calf thymus DNA (CT-DNA) by absorption titration, viscosity measurement, thermal melting, circular dichroism, ethidium bromide displacement assay and DNA cleavage of plasmid DNA (pBR322), investigated by gel electrophoresis. The dichlorido complexes bind covalently to DNA in the dark, similar to cisplatin, while the monochlorido complexes bind covalently on irradiation, similar to cisplatin analogues. The compounds are selectively cytotoxic against several tumour cell lines and show specific nonlinear correlation between dose and activity. This phenomenon is closely related to their potential to act preferentially as inhibitors of cell division.

Water soluble Ru(ii)–arene complexes of the antidiabetic drug metformin: DNA and protein binding, molecular docking, cytotoxicity and apoptosis-inducing activity

“…In contrast, decrease in viscosity is observed for 1 and 2 due to kinking or bending of the DNA helices upon covalent binding of complexes with DNA base pairs. A similar decrease in viscosity has been observed for [Ru(h 6 -p-cymene)(L)Cl](PF 6 ) (L ¼ N-(2-pyridylmethyl)glycine), 55 which is reported as a covalently DNA binding molecule. The decrease in viscosity is also observed for partially intercalating complex like [Ru(dmb) 2 (pdpt)](ClO 4 ) 2 (dmb ¼ 4,4 0 -dimethyl-2,2 0 -bipyridine, pdpt ¼ 3-(pyridine-2-yl)-5,6-diphenyl-astriazine).…”

“…57 The intercalating complexes rst unwind negatively supercoiled DNA and then convert it into positively supercoiled DNA. 55 The major/minor groove DNA binding and partial intercalating complexes convert the supercoiled DNA into nicked form, if one strand of DNA is cleaved 13 and linear form, if both strands are cleaved. 58 In order to explore the DNA interaction of 1 and 2, supercoiled (SC) pUC19 DNA (40 mM) was incubated with the complexes (100 mM) in 5 mM Tris-HCl/ 50 mM NaCl buffer (pH 7.1) at 37 C for 1 h in the absence of an activator.…”

Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action

“…Flow cytometry analyses were carried out on a CyFlow® Space instrument (from Sysmex Partec GmbH, Germany), equipped with five lasers (405, 488, 532, 561, 638–640 nm) and a charge‐coupled device (CCD) camera for sample flow monitoring. Results were analyzed with PartecFloMax® software, as reported previously …”

Synthesis, structure and antiproliferative activity of dinuclear ruthenium arene complexes with differently coordinated thiosemicarbazones

“…DNA is generally a potential target as with many metal‐based anticancer drugs, for DNA binding can lead to further ‘downstream’ effects and ultimately result in cell death . Therefore, the interactions of the representative A‐type complex 2 (and its corresponding B‐type complex 4 ) with p B R 322 plasmid DNA were investigated by agarose gel electrophoresis.…”