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Bis-picolinamide Ruthenium(III) Dihalide Complexes: Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity

Basri, Aida M., Lord, Rianne M., Allison, Simon J., Rodríguez-Bárzano, Andrea, Lucas, Stephanie J., Janeway, Felix D., Shepherd, Helena J., Pask, Christopher M., Phillips, Roger M., McGowan, Patrick C. and others. (2017) Bis-picolinamide Ruthenium(III) Dihalide Complexes: Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity. Chemistry - A European Journal, 23 (26). pp. 6341-6356. ISSN 0947-6539. E-ISSN 1521-3765. (doi:10.1002/chem.201605960) (KAR id:61698)

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Abstract

A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX2L2] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl2L2] complexes but upon a halide exchange reaction to yield [RuI2L2], only single trans isomers were detected. High cytotoxic activity against human cancer cell lines was observed, with the potencies of some complexes similar to or better than cisplatin. The conversion to [RuI2L2] substantially increased the activity towards cancer cell lines by more than twelvefold. The [RuI2L2] complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with a more than fourfold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, which indicates the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. The activity of selected complexes against non-cancer ARPE-19 cells was also tested. The [RuI2L2] complexes were found to be more potent than the [RuCl2L2] analogues and also more selective towards cancer cells with a selectivity factor in excess of sevenfold.

Item Type: Article
DOI/Identification number: 10.1002/chem.201605960
Divisions: Faculties > Sciences > School of Physical Sciences
Depositing User: Helena Shepherd
Date Deposited: 11 May 2017 13:19 UTC
Last Modified: 23 Jan 2020 04:13 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/61698 (The current URI for this page, for reference purposes)
Shepherd, Helena J.: https://orcid.org/0000-0003-0832-4475
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