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    Cytotoxicity and ROS production of novel Pt(IV) oxaliplatin derivatives with indole propionic acid

    Tolan, Dina and Almotairy, Awatif Rashed Z. and Howe, Orla and Devereux, Michael and Montagner, Diego and Erxleben, Andrea (2019) Cytotoxicity and ROS production of novel Pt(IV) oxaliplatin derivatives with indole propionic acid. Inorganica Chimica Acta, 492. pp. 262-267. ISSN 0020-1693

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    The coordination of biologically active moieties to the axial positions of Pt(IV) derivatives of Pt(II) anticancer drugs allows the co-delivery and simultaneous activation of two pro-drugs for combination therapy. Pt(IV) complexes with a redox modulator as an axial ligand can kill cancer cells by a mechanism combining DNA platination and generation of oxidative stress. In this study we evaluated the cytotoxicity of Pt(IV) complexes based on the oxaliplatin scaffold and the pro-oxidant indole-3-propionate in cisplatin-sensitive and cisplatinresistant ovarian cancer cells. A series of five complexes was synthesized and characterized by 1 H and 195Pt NMR spectroscopy, IR spectroscopy, mass spectrometry and elemental analysis; trans-[Pt(DACH)(ox)(IPA)(OH)] (1), trans-[Pt(DACH)(ox)(IPA)2] (2), trans-[Pt(DACH)(ox)(IPA)(bz)] (3), trans-[Pt(DACH)(ox)(IPA)(suc)] (4), and trans-[Pt(DACH)(ox)(IPA)(ac)] (5) (DACH = 1,2-diaminocyclohexane (1R,2R)-(−), ox = oxalate, IPA = indole3-propionate, bz = benzoate, suc = succinate and ac = acetate). The complexes were shown to produce cellular reactive oxygen species (ROS) in a time-dependent manner. The most potent ROS producer, complex 1, also elicited the highest cytotoxicity. Complex 1 was shown to form the mono- and bis-adducts [Pt(DACH)(guanosine)(OH)]+ and [Pt(DACH)(guanosine)2] 2+ in the presence of ascorbic acid, suggesting that on activation the released oxaliplatin will interact with DNA

    Item Type: Article
    Keywords: Oxaliplatin; Pt(IV) prodrugs; Redox stress; Indole propionic acid; Cytotoxicity;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 13923
    Identification Number:
    Depositing User: Diego Montagner
    Date Deposited: 02 Feb 2021 14:57
    Journal or Publication Title: Inorganica Chimica Acta
    Publisher: Elsevier
    Refereed: Yes
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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