Biological properties of a new mixed lanthanide(III) complex incorporating a dypiridinium ylide

Fernanda Marujo Marques; Mendes F.; Paula Cabral Campello, Maria

Informações chave

Autores:

Fernanda Marujo Marques (Fernanda Marujo Marques); Mendes F. (Filipa Fernandes Mendes); Paula Cabral Campello, Maria (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros)

Publicado em

01/06/2020

Resumo

A new mixed lanthanide(III) complex [LaNd(μ2-DPY)(μ4-SO4)2(Et3N)]Br2·2H2OMeOH (La-Nd-DPY) was obtained by the reaction of N,N′-diphenacyl-4,4′-dipyridinium dibromide (DPB) with a mixture of La(III) and Nd(III) sulfates in a 2:1 M ratio, in the presence of triethylamine (Et3N). The method used for the synthesis of La-Nd-DPY promoted the in situ transformation of the pro-ligand DPB into the dipyridinium ylide-based ligand. Fourier transform infrared spectroscopy (FTIR), elemental analysis (EA), thermogravimetric analysis (TGA) and mass spectrometry (MS) concurred to propose a linear polymeric structure for La-Nd-DPY, in which both La(III) and Nd(III) ions are six-coordinated. Cyclic voltammetry was also used to assess the redox potential of the mixed complex. Scanning electron microscopy (SEM) showed quite uniform and homogeneous fibrillary net-like morphology and also confirmed, by means of EDX analysis, the presence of both lanthanide (III) ions in the mixed complex. UV–vis absorption spectroscopy demonstrated that the mixed Ln complex is stable up to 1 h in DMSO and up to 72 h under the physiological conditions used for cell culture. The cytotoxic activity of La-Nd-DPY in cancer cell lines of ovarian (A2780), breast (MCF7) and prostate (PC3) origins and in multicellular tumor spheroids derived from PC3 cells was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and acid phosphatase (APH) assays. Compared to cisplatin this new complex showed improved toxicity, with IC50 values at least 10 times higher, even at 24 h of exposure. The cytotoxic effects seemed to be mediated by reactive oxygen species (ROS) generation but not apoptosis, confirmed by a caspase-3/7 activation and Hoechst nuclei staining assays. The mechanism of cell death observed on the cytotoxicity assays is probably due to other pathways of cell death, which deserve to be further investigated.