Multinuclear ruthenium(II) complexes as anticancer agents

Gorle, Anil K., Ammit, Alaina J., Wallace, Lynne, Keene, F. Richard, and Collins, J. Grant (2014) Multinuclear ruthenium(II) complexes as anticancer agents. New Journal of Chemistry, 38. pp. 4049-4059.

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Abstract

A series of dinuclear ruthenium(II) complexes that contain labile chlorido ligands, [{Ru(tpy)Cl}2{mu-bbn}]2+ {designated Cl-Rubbn; tpy = 2,2':6',2''-terpyridine, bbn = bis[4(40-methyl-2,20-bipyridyl)]-1,n-alkane (n = 7, 10, 12, 14 or 16)} and derivatives containing nitro substituents on the tpy ligand and/or secondary amines within the bbn linking chain have been synthesised and their potential as anticancer agents examined. Some of the Cl-Rubbn species showed good anticancer activity against MCF-7 and MDA-MB- 231 breast cancer cell lines, with the Cl-Rubb12 complex being four-times more active than cisplatin. Inclusion of nitro substituents on the tpy ligands of Cl-Rubb12 resulted in significantly decreased anticancer activity. The incorporation of amine groups into the linking ligand did not increase the anticancer activity of the Cl-Rubbn complexes. The Cl-Rubbn complexes and those containing amine groups in the linking chain aquated at approximately the same rate, with 50% aquation within 120 minutes. By comparison, the complexes containing nitro substituents on the tpy ligand aquated extremely slowly, with 60% of the chlorido complex remaining 24 hours after they were dissolved in water. Cyclic voltammetry with the model mononuclear complex [Ru{(NO2)3tpy}(Me2bpy)Cl]+ {(NO2)3tpy = 4,40,400- trinitro-2,20:60,200-terpyridine} showed that the nitro substituents exerted a strong effect on the ruthenium centre, with the anodic peak corresponding to the Ru(III/II) couple shifted positively by 300 mV compared to that from the non-nitrated parent complex [Ru(tpy)(Me2bpy)Cl]+. 1H NMR studies of the reaction of the Cl-Rubbn complexes with GMP indicated that the ruthenium complexes covalently bound the nucleotide slowly, with 33% bound in 24 hours. However, the results of this study suggest that the cytotoxicity of the binuclear ruthenium complexes is a combination of covalent and reversible binding with DNA.

Item ID: 33516
Item Type: Article (Research - C1)
ISSN: 1369-9261
Keywords: anticancer; mutinuclear; ruthenium; labile complexes
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This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Date Deposited: 24 Jun 2014 00:46
FoR Codes: 03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030201 Bioinorganic Chemistry @ 80%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110801 Medical Bacteriology @ 20%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
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