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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

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    Publication date
    2017-05-05
    Author
    Basri, A.M.
    Lord, Rianne M.
    Allison, Simon J.
    Rodríguez-Bárzano, A.
    Lucas, S.J.
    Janeway, F.X.
    Shepherd, H.J.
    Pask, C.M.
    Phillips, Roger M.
    McGowan, P.C.
    Keyword
    Anti-cancer; Cytotoxicity; Isomers; Ruthenium(III); Trans-compounds
    Rights
    © 2017 Wiley. This is the peer-reviewed version of the following article: Basri AM, Lord RM, Allison SJ et al (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): 6341-6356, which has been published in final form at http://dx.doi.org/10.1002/chem.201605960. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
    Peer-Reviewed
    Yes
    
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    Abstract
    A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type RuX2L2 (X = Cl or I and L = picolinamide) have been synthesised and characterised. They exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies reveal a mixture of cis and trans isomers for the RuCl2L2 complexes but upon a halide exchange reaction to RuI2L2, only single trans isomers are present. High cytotoxic activity against human cancer cell lines was observed, with potencies for some complexes similar to or better than cisplatin. Conversion to RuI2L2 substantially increased activity towards cancer cell lines by >12-fold. The RuI2L2 complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with >4-fold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, indicating the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. Selected complexes were also tested against non-cancer ARPE-19 cells. The RuI2L2 complexes are more potent than the RuCl2L2 analogues, and also more selective towards cancer cells with a selectivity factor >7-fold.
    URI
    http://hdl.handle.net/10454/11550
    Version
    Accepted Manuscript
    Citation
    Basri AM, Lord RM, Allison SJ et al (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): 6341-6356.
    Link to publisher’s version
    http://dx.doi.org/10.1002/chem.201605960
    Type
    Article
    Collections
    Life Sciences Publications

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