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    β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding

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    Publication date
    2016-12-01
    Author
    Lord, Rianne M.
    Mannion, J.J.
    Crossley, B.D.
    Hebden, A.J.
    McMullon, M.W.
    Fisher, J.
    Phillips, Roger M.
    McGowan, P.C.
    Keyword
    β-Diketonate titanium compounds; Crystal structures; Cytotoxicity; DNA binding
    Rights
    © 2016 John Wiley and Sons. The full-text has been reproduced in accordance with the publisher's self-archiving policy.
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    Herein, we report 31 new β-diketonate titanium compounds of the type [Ti(O,O)2X2], whereby O,O = asymmetric or symmetric β-diketonate ligand and X = Cl, Br, OEt or OiPr. Thirteen new crystal structures are discussed and show that these octahedral species all adopt cis geometries in the solid state. These compounds have been tested for their cytotoxicity using SRB and MTT assays, showing several of the compounds are as potent as cisplatin against a range of tumour cell lines. Results also show the [Ti(O,O)2Br2] complexes are more potent than [Ti(O,O)2Cl2], [Ti(O,O)2(OEt)2] and [Ti(O,O)2(OiPr)2]. Using a simple symmetrical heptane-3,5-dione (O,O) ligand bound to titanium, we observed more than a 50-fold increase in potency with the [Ti(O,O)2Br2] (28) when compared to [Ti(O,O)2Cl2] (27). One of the more potent compounds (6) has been added to three different sixmers of DNA, in order to analyse the potential DNA binding of the compound. NMR studies have been carried out on the compounds, in order to understand the structural properties and the species formed in solution during the in vitro cell assays.
    URI
    http://hdl.handle.net/10454/10871
    Version
    Accepted Manuscript
    Citation
    Lord RM, Mannion JJ, Crossley BD et al (2016) β-Diketonate Titanium Compounds Exhibiting High In Vitro Activity and Specific DNA Base Binding. ChemistrySelect. 1(20): 6598-6605.
    Link to publisher’s version
    http://dx.doi.org/10.1002/slct.201601290
    Type
    Article
    Collections
    Life Sciences Publications

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