Synthesis, characterization and biological activity of new cyclometallated platinum(iv) iodido complexes.
Dalton Trans
; 46(43): 14973-14987, 2017 Nov 07.
Article
em En
| MEDLINE
| ID: mdl-29048088
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)2N(CH2)3NCH(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, IIα, 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 1H NMR experiments. Remarkable topoisomerase IIα 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).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Platina
/
Complexos de Coordenação
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article