Browsing by Author "Pinheiro, Teresa"
Now showing 1 - 4 of 4
Results Per Page
Sort Options
- Copper Complexes with 1,10-Phenanthroline Derivatives: Underlying Factors Affecting Their CytotoxicityPublication . Nunes, Patrique; Correia, Isabel; Marques, Fernanda; Matos, Antonio Pedro; dos Santos, Margarida M. C.; Azevedo, Cristina G.; Capelo, Jose-Luis; Santos, Hugo M.; Gama, Sofia; Pinheiro, Teresa; Cavaco, Isabel; Pessoa, Joao CostaThe interpretation of in vitro cytotoxicity data of Cu(II)-1,10-phenanthroline (phen) complexes normally does not take into account the speciation that complexes undergo in cell incubation media and its implications in cellular uptake and mechanisms of action. We synthesize and test the activity of several distinct Cu(II)-phen compounds; up to 24 h of incubation, the cytotoxic activity differs for the Cu complexes and the corresponding free ligands, but for longer incubation times (e.g., 72 h), all compounds display similar activity. Combining the use of several spectroscopic, spectrometric, and electrochemical techniques, the speciation of Cu-phen compounds in cell incubation media is evaluated, indicating that the originally added complex almost totally decomposed and that Cu(II) and phen are mainly bound to bovine serum albumin. Several methods are used to disclose relationships between structure, activity, speciation in incubation media, cellular uptake, distribution of Cu in cells, and cytotoxicity. Contrary to what is reported in most studies, we conclude that interaction with cell components and cell death involves the separate action of Cu ions and phen molecules, not [Cu(phen)(n)] species. This conclusion should similarly apply to many other Cu-ligand systems reported to date.
- Metallothionein levels in Algerian mice (Mus spretus) exposed to elemental pollution: an ecophysiological approachPublication . Marques, Carla Cristina; Gabriel, Sofia Isabel; Pinheiro, Teresa; Viegas-Crespo, Ana Maria; Mathias, Maria da Luz; Bebianno, Maria JoãoThe potential use of metallothioneins (MTs) as biomarkers of trace metal contamination was evaluated for the first time in the Algerian mouse (Mus spretus). Mice were collected seasonally in an abandoned mining area (Aljustrel) and in a reference area, both located in southern Portugal. MT levels were quantified in liver and kidney by differential pulse polarography and hepatic elemental concentrations (Mn, Fe, Cu, Zn, Se) were determined by particle-induced X-ray emission. Hepatic iron and selenium concentrations were elevated in mice from Aljustrel mine when compared to reference animals. MTs levels were averagely higher in mice from Aljustrel than those originated from the reference area. A season-dependent significant effect was found on the hepatic and renal MT concentrations, characterized by higher levels in winter and lower in autumn. In contaminated mice positive relationship between liver elemental contents (Cu in autumn and Fe in winter) and MTs were found. The seasonal variation of MT suggests that probably physiological and environmental factors could influence hepatic and renal MT induction. Results seem to imply that some environmental disturbance occur in the vicinity of the Aljustrel mine. Therefore, for the management purposes MT levels should be followed in liver of M. spretus, especially in winter. Furthermore, other physiological factors that could influence MT expression and turnover in Algerian mouse should also be monitored.
- New Cu(II) complexes with pyrazolyl derived schiff base ligands: synthesis and biological evaluationPublication . Ribeiro, Nadia; Roy, Somnath; Butenko, Nataliya; Cavaco, Isabel; Pinheiro, Teresa; Alho, Irina; Marques, Fernanda; Avecilla, Fernando; Pessoa, Joao Costa; Correia, IsabelSince the discovery of cisplatin there has been a continuous pursuit for new metallodrugs showing higher efficacies and lower side effects. In this work, new copper(II) complexes (C1-C6) of Schiff bases derived from pyrazolyl were developed. Through condensation of 5-methyl-1H-pyrazole-3-carbohydrazide with different aromatic aldehydes - pyridoxal, salicylaldehyde, 3-methoxy-2-hydroxybenzaldehyde, 3-ethoxy-2-hydroxybenzaldehyde and 2-hydroxynaphthene-l-carbaldehyde a set of new pyrazole based "ONO" tridentate Schiff bases were obtained in moderate to good yields - L1-L6, as well as their Cu(II)-complexes. All compounds were characterized by analytical techniques and their molecular formulae established. The antioxidant potential of all compounds was tested, yielding low activity in most cases, with the exception of L1 and C5. The Cu(II) complexes were tested for their aqueous stability, and for their interaction with biological molecules, namely DNA and HSA (human serum albumin), through fluorescence quenching experiments (and electrophoresis for DNA). With the exception of C3, all the synthesized complexes were able to interact with DNA and HSA. Their cytotoxic activity against two cancer cell lines (MCF7 - breast and PC3 - prostate) was also evaluated. Complexes C5 and C6, with larger aromatic systems, showed much higher cytotoxicity (in the low mu M range), than C1-C4, as well as IC50 values much lower than cisplatin. For C6 the results suggest that the mechanisms of cell death do not seem to be mediated by apoptosis, through caspases 3/7 activation, but by involving membrane potential and imbalance in physiological elements such as P, K and Ca.
- Therapeutic potential of vanadium complexes with 1,10-phenanthroline ligands, quo vadis? Fate of complexes in cell media and cancer cellsPublication . Nunes, Patrique; Correia, Isabel; Cavaco, Isabel; Marques, Fernanda; Pinheiro, Teresa; Avecilla, Fernando; Pessoa, Joao Costa(VO)-O-IV-complexes formulated as [(VO)-O-IV(OSO3)(phen)(2)] (1) (phen = 1,10-phenanthroline), [(VO)-O-IV(OSO3) (Me(2)phen)(2)] (2) (Me(2)phen = 4,7-dimethyl-1,10-phenanthroline) and [(VO)-O-IV(OSO3)(amphen)(2)] (3) (amphen = 5-amino-1,10-phenanthroline) were prepared and stability in cell incubation media evaluated. Their cytotoxicity was determined against the A2780 (ovarian), MCF7 (breast) and PC3 (prostate) human cancer cells at different incubation times. While at 3 and 24 h the cytotoxicity differs for complexes and corresponding free ligands, at 72 h incubation all compounds are equally active presenting low IC50 values. Upon incubation of A2780 cells with 1-3, cellular distribution of vanadium in cytosol, membranes, nucleus and cytoskeleton, indicate that the uptake of V is low, particularly for 1, and that the uptake pattern depends on the ligand. Nuclear microscopic techniques are used for imaging and elemental quantification in whole PC3 cells incubated with 1. Once complexes are added to cell culture media, they decompose, and with time most V-IV oxidizes to V-V-species. Modeling of speciation when [(VO)-O-IV(OSO3)(phen)(2)] (1) is added to cell media is presented. At lower concentrations of 1, (VO)-O-IV- and phen-containing species are mainly bound to bovine serum albumin, while at higher concentrations [(VO)-O-IV (phen)n](2+)-complexes become relevant, being predicted that the species taken up and mechanisms of action operating depend on the total concentration of complex. This study emphasizes that for these (VO)-O-IV-systems, and probably for many others involving oxidovanadium or other labile metal complexes, it is not possible to identify active species or propose mechanisms of cytotoxic action without evaluating speciation occurring in cell media.