Bauer, EmmaDomingo, XavierBalcells, C.Polat, Ibrahim H.Crespo Vicente, Margarita Ma.Quirante Serrano, JosefinaBadía Palacín, JosefaBaldomà Llavinés, LauraFont Bardia, Ma. MercedesCascante i Serratosa, Marta2020-05-312020-05-312017-11-211477-9226https://hdl.handle.net/2445/163390The synthesis of six novel cyclometallated platinum(IV) iodido complexes is accomplished by intermolecular oxidative addition of methyl iodide (compounds 2a-2c) or iodine (compounds 3a-3c) upon cyclometallated platinum(II) compounds [PtX{(CH3)(2)N(CH2)(3)NCH(4-ClC6H3)}] (1a-1c: X = Cl, CH3 or I). The X-ray molecular structures of platinum(II) compound 1c and platinum(IV) compounds 3b and 3a' (an isomer of 3a) are reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), DNA interaction, topoisomerase I, II alpha, and cathepsin B inhibition, and cell cycle arrest, apoptosis and ROS generation of the investigated complexes are presented. Remarkable antiproliferative activity was observed for most of the synthesized cycloplatinated compounds (series 1-3) in all the selected carcinoma cell lines. The best inhibition was provided for the octahedral platinum(IV) compounds 2a-2c exhibiting a methyl and an iodido axial ligand. Preliminary biological results point to a different mechanism of action for the investigated compounds. Cyclometallated platinum(II) compounds 1a-1c modify the DNA migration as cisplatin. In contrast, cyclometallated platinum(IV) compounds 2a-2c and 3a-3c did not modify the DNA tertiary structure neither in the absence nor in the presence of ascorbic acid, which made them incapable of reducing platinum(IV) compounds 2b and 2c in a buffered aqueous medium (pH 7.40) according to H-1 NMR experiments. Remarkable topoisomerase II alpha inhibitory activity is reported for platinum(IV) complexes 2b and 3a and in addition, for the last one, a moderate cathepsin B inhibition is reported. Cell cycle arrest (decrease in G0/G1 and G2 phases and arrest in the S phase), induction of apoptosis and ROS generation are related to the antiproliferative activity of some representative octahedral cyclometallated platinum(IV) compounds (2b and 2c).45 p.application/pdfeng(c) Bauer, Emma et al., 2017PlatíMetallsPlatinumMetalsinfo:eu-repo/semantics/article6776192020-05-31info:eu-repo/semantics/openAccess