Browsing by Author "Ribeiro, Nadia"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- Interaction of [(VO)-O-IV(acac)(2)] with Human Serum Transferrin and AlbuminPublication . Correia, Isabel; Chorna, Ielyzaveta; Cavaco, Isabel; Roy, Somnath; Kuznetsov, Maxim L.; Ribeiro, Nadia; Justino, Goncalo; Marques, Fernanda; Santos-Silva, Teresa; Santos, Marino F. A.; Hugo, M. Santos E.; Capelo, Jose L.; Doutch, James; Pessoa, Joao CostaVO(acac)(2)] is a remarkable vanadium compound and has potential as a therapeutic drug. It is important to clarify how it is transported in blood, but the reports addressing its binding to serum proteins have been contradictory. We use several spectroscopic and mass spectrometric techniques (ESI and MALDI-TOF), small-angle X-ray scattering and size exclusion chromatography (SEC) to characterize solutions containing [VO(acac)(2)] and either human serum apotransferrin (apoHTF) or albumin (HSA). DFT and modeling protein calculations are carried out to disclose the type of binding to apoHTF. The measured circular dichroism spectra, SEC and MALDI-TOF data clearly prove that at least two VOacac moieties may bind to apoHTF, most probably forming [(VO)-O-IV(acac)(apoHTF)] complexes with residues of the HTF binding sites. No indication of binding of [VO(acac)(2)] to HSA is obtained. We conclude that (VO)-O-IV-acac species may be transported in blood by transferrin. At very low complex concentrations speciation calculations suggest that [(VO)(apoHTF)] species form.
- Naphthoylhydrazones: coordination to metal ions and biological screeningPublication . Ribeiro, Nadia; Galvao, Adelino M.; Gomes, Clara S. B.; Ramos, Helena; Pinheiro, Rute; Saraiva, Lucilia; Ntungwe, Epole; Isca, Vera; Rijo, Patricia; Cavaco, Isabel; Ramilo-Gomes, Filipa; Guedes, Rita C.; Pessoa, Joao Costa; Correia, IsabelWe report the synthesis of 3-hydroxyl-2-naphthoylhydrazones containing pyrrole (HL1), furane (HL2) and thiophene (HL3) moieties and their V(IV)O-, Cu(II)- and Zn(II)-complexes. All compounds are characterized by the usual analytical techniques and coordination of the ligands to the metal ions is discussed based on spectroscopic data (FTIR, UV-vis, EPR and NMR) as well as CAMB3LYP DFT/TDDFT calculations, indicating the formation of neutral ML2 type complexes. The photophysical properties of ligands and complexes are disclosed. The binding to Bovine Serum Albumin (BSA) is evaluated in detail using several spectroscopic tools. Circular dichroism shows that the compounds, and particularly the ligand precursors, stabilize BSA, increasing its a-helical content. Fluorescence studies indicate the formation of 1 : 1 protein-compound adducts, which is corroborated by molecular docking studies that show the interaction between Trp 213 of BSA and the naphthalene rings. The general toxicity is evaluated using the Artemia salina lethality assay, with all compounds showing general toxicity towards the brine shrimp model. The cytotoxicity on human cancer cells (H1299, MCF7, and HCT116) is assessed for all compounds and the half-maximal inhibitory concentration (IC50) values are in the range from 0.57 to 27.35 mu M. Compounds containing L-1 (pyrrole derivative) are the most cytotoxic, with the vanadium and zinc complexes performing better than the copper ones, and some of them depicting IC50 values lower than 1.1 mM. However, selectivity needs improvement as the compounds show toxicity towards Artemia salina and normal fibroblasts.
- 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.