Please use this identifier to cite or link to this item:
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
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:
It is part of: Dalton Transactions, 2017, vol. 46, num. 43, p. 14973-14987
Related resource:
ISSN: 1477-9226
Appears in Collections:Articles publicats en revistes (Mineralogia, Petrologia i Geologia Aplicada)

Files in This Item:
File Description SizeFormat 
677619.pdf1.98 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.