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http://hdl.handle.net/2445/163390
Title: | Synthesis, characterization and biological activity of new cyclometallated platinum(IV) iodido complexes |
Author: | Bauer, Emma Domingo, Xavier Balcells, C. Polat, Ibrahim H. Crespo Vicente, Margarita Ma. Quirante Serrano, Josefina Badía Palacín, Josefa Baldomà Llavinés, Laura Font Bardia, Ma. Mercedes Cascante i Serratosa, Marta |
Keywords: | Platí Metalls Platinum Metals |
Issue Date: | 21-Nov-2017 |
Publisher: | Royal Society of Chemistry |
Abstract: | The 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). |
Note: | Versió postprint del document publicat a: https://doi.org/10.1039/c7dt03448b |
It is part of: | Dalton Transactions, 2017, vol. 46, num. 43, p. 14973-14987 |
URI: | http://hdl.handle.net/2445/163390 |
Related resource: | https://doi.org/10.1039/c7dt03448b |
ISSN: | 1477-9226 |
Appears in Collections: | Articles publicats en revistes (Mineralogia, Petrologia i Geologia Aplicada) |
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