RESUMO
Three novel copper complexes with tridentate N2O ligand di(2-pyridil) ketone 1-adamantoyl hydrazone (Addpy) of the formula [Cu(II)2Cu(I)2(Addpy)2Br2(µ-Br4)] (1), catena-poly[CuCl(µ-Addpy)(µ-Cl)CuCl2]n (2) and [Cu(Addpy)(NCS)2] (3) were synthesized. Complexes are characterized by X-ray crystallography, spectral (UV-Vis, FTIR), electrochemical (CV) analyses, and magnetochemical measurements. Investigation of anticancer potential of Cu(II) complexes, mode of cell death, apoptosis, and inhibition of angiogenesis were performed. All tested malignant cell lines (HeLa, LS174, A549, K562, and MDA-MB-231) showed high sensitivity to the examined Cu(II) complexes. It has been shown that the complexes induce apoptosis in the caspase 3-dependent manner, whereas the anti-angiogenic effects of 1, 2, and 3 have been confirmed in EA.hy926 cells using a tube formation assay.
Assuntos
Adamantano/análogos & derivados , Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Cobre/farmacologia , Hidrazonas/farmacologia , Neovascularização Patológica/tratamento farmacológico , Compostos Organometálicos/farmacologia , Piridinas/farmacologia , Adamantano/química , Adamantano/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hidrazonas/química , Estrutura Molecular , Neovascularização Patológica/patologia , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Piridinas/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Two different types of magnetic nanoparticles (MNPs) were synthesized in order to compare their efficiency as radioactive vectors, Fe3O4-Naked (80 ± 5 nm) and polyethylene glycol 600 diacid functionalized Fe3O4(Fe3O4-PEG600) MNPs (46 ± 0.6 nm). They were characterized based on the external morphology, size distribution, and colloidal and magnetic properties. The obtained specific power absorption value for Fe3O4-PEG600 MNPs was 200 W/g, indicated their potential in hyperthermia based cancer treatments. The labeling yield, in vitro stability and in vivo biodistribution profile of (90) Y-MNPs were compared. Both types of MNPs were (90)Y-labeled in reproducible high yield (>97%). The stability of the obtained radioactive nanoparticles was evaluated in saline and human serum media in order to optimize the formulations for in vivo use. The biodistribution in Wistar rats showed different pharmacokinetic behaviors of nanoparticles: a large fraction of both injected MNPs ended in the liver (14.58%ID/g for (90)Y-Fe3O4-Naked MNPs and 19.61%ID/g for (90)Y-Fe3O4-PEG600 MNPs) whereas minor fractions attained in other organs. The main difference between the two types of MNPs was the higher accumulation of (90)Y-Fe3O4-Naked MNPs in the lungs (12.14%ID/g vs. 2.00%ID/g for (90)Y-Fe3O4-PEG600 MNPs) due to their in vivo agglomeration. The studied radiolabeled magnetic complexes such as (90)Y-Fe3O4-PEG600 MNPs constitute a great promise for multiple diagnostic-therapeutic uses combining, for example, MRI-magnetic hyperthermia and regional radiotherapy.