Antiproliferative activity of ruthenium(ii) arene complexes with mono- and bidentate pyridine-based ligands.
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.
Universität Leipzig, Institut für Anorganische Chemie, Johannisallee 29, 04103 Leipzig, Germany. hey@uni-leipzig.de.
Stefan
S
Richter
Department of Chemistry, Savitribai Phule Pune University, Pune-411007, India.
Sushma
S
Singh
Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Dijana
D
Draca
Department of Chemistry, Savitribai Phule Pune University, Pune-411007, India.
Anup
A
Kate
Department of Chemistry, Savitribai Phule Pune University, Pune-411007, India.
Anupa
A
Kumbhar
Department of Chemistry, Savitribai Phule Pune University, Pune-411007, India.
Avinash S
AS
Kumbhar
Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Danijela
D
Maksimovic-Ivanic
Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Sanja
S
Mijatovic
Universität Leipzig, Institut für Anorganische Chemie, Johannisallee 29, 04103 Leipzig, Germany. hey@uni-leipzig.de.
Peter
P
Lönnecke
Universität Leipzig, Institut für Anorganische Chemie, Johannisallee 29, 04103 Leipzig, Germany. hey@uni-leipzig.de.
Evamarie
E
Hey-Hawkins
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D053837:DNA Cleavage; D006801:Humans; D008024:Ligands; D010957:Plasmids; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D011725:Pyridines; D012428:Ruthenium; D004247:DNA; C427203:calf thymus DNA