Elene C. Pereira-Maia
Universidade Federal de Minas Gerais
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Featured researches published by Elene C. Pereira-Maia.
Inorganic Chemistry | 2011
Priscila P. Silva; Wendell Guerra; Josiane N. Silveira; Ana Maria da Costa Ferreira; Tiago Bortolotto; Franciele L. Fischer; Hern an Terenzi; Ademir Neves; Elene C. Pereira-Maia
This paper reports on the synthesis and characterization of two new ternary copper(II) complexes: [Cu(doxycycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (1) and [Cu(tetracycline)(1,10-phenanthroline)(H(2)O)(ClO(4))](ClO(4)) (2). These compounds exhibit a distorted tetragonal geometry around copper, which is coordinated to two bidentate ligands, 1,10-phenanthroline and tetracycline or doxycyline, a water molecule, and a perchlorate ion weakly bonded in the axial positions. In both compounds, copper(II) binds to tetracyclines via the oxygen of the hydroxyl group and oxygen of the amide group at ring A and to 1,10-phenanthroline via its two heterocyclic nitrogens. We have evaluated the binding of the new complexes to DNA, their capacity to cleave it, their cytotoxic activity, and uptake in tumoral cells. The complexes bind to DNA preferentially by the major groove, and then cleave its strands by an oxidative mechanism involving the generation of ROS. The cleavage of DNA was inhibited by radical inhibitors and/or trappers such as superoxide dismutase, DMSO, and the copper(I) chelator bathocuproine. The enzyme T4 DNA ligase was not able to relegate the products of DNA cleavage, which indicates that the cleavage does not occur via a hydrolytic mechanism. Both complexes present an expressive plasmid DNA cleavage activity generating single- and double-strand breaks, under mild reaction conditions, and even in the absence of any additional oxidant or reducing agent. In the same experimental conditions, [Cu(phen)(2)](2+) is approximately 100-fold less active than our complexes. These complexes are among the most potent DNA cleavage agents reported so far. Both complexes inhibit the growth of K562 cells with the IC(50) values of 1.93 and 2.59 μmol L(-1) for compounds 1 and 2, respectively. The complexes are more active than the free ligands, and their cytotoxic activity correlates with intracellular copper concentration and the number of Cu-DNA adducts formed inside cells.
Química Nova | 2010
Elene C. Pereira-Maia; Priscila P. Silva; Wagner B. De Almeida; Hélio F. Dos Santos; Bruna L. Marcial; Reinaldo Ruggiero; Wendell Guerra
Tetracyclines exhibits activity to a broad range of Gram-negative and Gram-positive bacteria and this fact allied to the low toxicity, low cost, and the advantage of administration by oral route led to their indiscriminate use, which caused the appearance of bacterial resistance to these agents, wich has restricted its clinical utility, though new applications have emerged. On the other hand, the glycylcyclines, semi-synthetic products are similar to tetracyclines, which are active against many bacteria resistant to tetracycline and other classes of antibiotics. The purpose of this paper is to give an overview of this important class of antibiotics focusing on its coordination chemistry and possible applications.
Journal of Inorganic Biochemistry | 2009
Nicolás A. Rey; Ademir Neves; Priscila P. Silva; Flávia C.S. de Paula; Josianne Nicácio Silveira; Françoise V. Botelho; Leda Quercia Vieira; Claus Tröger Pich; Hernán Terenzi; Elene C. Pereira-Maia
We have studied the protonation equilibria of a dicopper(II) complex [Cu(2)(micro-OH)(C(21)H(33)ON(6))](ClO(4))(2).H(2)O, (1), in aqueous solution, its interactions with DNA, its cytotoxic activity, and its uptake in tumoral cells. C(21)H(33)ON(6) corresponds to the ligand 4-methyl-2,6-bis[(6-methyl-1,4-diazepan-6-yl)iminomethyl]phenol. From spectrophotometric data the following pKa values were calculated 3.27, 4.80 and 6.10. Complex 1 effectively promotes the hydrolytic cleavage of double-strand plasmid DNA under anaerobic and aerobic conditions. The following kinetic parameters were calculated k(cat) of 2.73 x 10(-4)s(-1), K(M) of 1.36 x 10(-4)M and catalytic efficiency of 2.01 s(-1)M(-1), a 2.73 x 10(7) fold increase in the rate of the reaction compared to the uncatalyzed hydrolysis rate of DNA. Competition assays with distamycin reveal minor groove binding. Complex 1 inhibited the growth of two tumoral cell lines, GLC4 and K562, with the IC(50) values of 14.83 microM and 34.21 microM, respectively. There is a good correlation between cell growth inhibition and intracellular copper content. When treated with 1, cells accumulate approximately twice as much copper as with CuCl(2). Copper-DNA adducts are formed inside cells when they are exposed to the complex. In addition, at concentrations that compound 1 inhibits tumoral cell growth it does not affect macrophage viability. These results show that complex 1 has a good therapeutic prospect.
Inorganic Chemistry | 2011
Tiago Bortolotto; Priscila P. Silva; Ademir Neves; Elene C. Pereira-Maia; Hernán Terenzi
In this report, we demonstrate how UV-light exposure can enhance DNA cleavage promoted by two copper(II) complexes of tetracyclines and 1,10-phenanthroline about 40 times in comparison to nonirradiated conditions. In addition, new aspects regarding their DNA binding properties, as well as the mechanism of the cleavage reaction, were also investigated.
Journal of Inorganic Biochemistry | 2014
Priscila P. Silva; Wendell Guerra; Geandson Coelho dos Santos; Nelson G. Fernandes; Josiane N. Silveira; Ana Maria da Costa Ferreira; Tiago Bortolotto; Hernán Terenzi; Adailton J. Bortoluzzi; Ademir Neves; Elene C. Pereira-Maia
Four new ternary complexes of copper(II) were synthesized and characterized: [Cu(hyd)(bpy)(acn)(ClO4)](ClO4)] (1), [Cu(hyd)(phen)(acn)(ClO4)](ClO4)] (2), [Cu(Shyd)(bpy)(acn)(ClO4)](ClO4)] (3) and [Cu(Shyd)(phen)(acn)(ClO4)](ClO4)] (4), in which acn=acetonitrile; hyd=2-furoic acid hydrazide, bpy=2,2-bipyridine; phen=1,10-phenanthroline and Shyd=2-thiophenecarboxylic acid hydrazide. The cytotoxic activity of the complexes in a chronic myelogenous leukemia cell line was investigated. All complexes are able to enter cells and inhibit cellular growth in a concentration-dependent manner, with an activity higher than that of the corresponding free ligands. The substitution of Shyd for hyd increases the activity, while the substitution of bpy for phen renders the complex less active. Therefore, the most potent complex is 4 with an IC50 value of 1.5±0.2μM. The intracellular copper concentration needed to inhibit 50% of cell growth is approximately 7×10(-15)mol/cell. It is worth notifying that a correlation between cytotoxic activity, DNA binding affinity and DNA cleavage was found: 1<3<2<4.
Brazilian Journal of Medical and Biological Research | 2007
A.D. Carvalho Júnior; F.P. Vieira; V.J. De Melo; M.T.P. Lopes; Josianne Nicácio Silveira; Gilson Andrade Ramaldes; Arlette Garnier-Suillerot; Elene C. Pereira-Maia; M. C. de Oliveira
We encapsulated cisplatin into stealth pH-sensitive liposomes and studied their stability, cytotoxicity and accumulation in a human small-cell lung carcinoma cell line (GLC4) and its resistant subline (GLC4/CDDP). Since reduced cellular drug accumulation has been shown to be the main mechanism responsible for resistance in the GLC4/CDDP subline, we evaluated the ability of this new delivery system to improve cellular uptake. The liposomes were composed of dioleoylphosphatidylethanolamine (DOPE), cholesteryl hemisuccinate (CHEMS), and distearoylphosphatidylethanolamine-polyethyleneglycol 2000 (DSPE-PEG2000) and were characterized by determining the encapsulation percentage as a function of lipid concentration. Among the different formulations, DOPE/CHEMS/DSPE-PEG liposomes (lipid concentration equal to 40 mM) encapsulated cisplatin more efficiently than other concentrations of liposomes (about 20.0%, mean diameter of 174 nm). These liposomes presented good stability in mouse plasma which was obtained using a 0.24-M EDTA solution (70% cisplatin was retained inside the liposomes after 30 min of incubation). Concerning cytotoxic effects, they are more effective (1.34-fold) than free cisplatin for growth inhibition of the human lung cancer cell line A549. The study of cytotoxicity to GLC4 and GLC4/CDDP cell lines showed similar IC50 values (approximately 1.4 microM), i.e., cisplatin-resistant cells were sensitive to this cisplatin formulation. Platinum accumulation in both sensitive and resistant cell lines followed the same pattern, i.e., approximately the same intracellular platinum concentration (4.0 x 10-17 mol/cell) yielded the same cytotoxic effect. These results indicate that long-circulating pH-sensitive liposomes, also termed as stealth pH-sensitive liposomes, may present a promising delivery system for cisplatin-based cancer treatment. This liposome system proved to be able to circumvent the cisplatin resistance, whereas it was not observed when using non-long-circulating liposomes composed of phosphatidylcholine, phosphatidylserine, and cholesterol.
Journal of Inorganic Biochemistry | 1999
Flávia C.S. de Paula; Sandra Carvalho; Hélio A. Duarte; Eucler B. Paniago; Antonio S. Mangrich; Elene C. Pereira-Maia
The interaction of tetracycline and oxovanadium(IV) in aqueous solution was studied by potentiometric and spectrophotometric methods. Oxovanadium(IV) ions form both a positively charged 1:1 and a neutral 2:1 metal-ligand complex with tetracycline. When a 1:1 ligand-to-metal ratio mixture is used at about pH 4.5 the 1:1 species predominates, being replaced at pH 6 by the binuclear complex. The binuclear complex has been isolated and fully characterised. Infrared and EPR studies suggest the existence of two distinct vanadyl binding sites. Our results indicate that the first vanadium coordinates to the BCD-ring system and the second one to the A-ring. Biological implications of the existence of a neutral complex at physiological pH are briefly discussed.
Journal of Inorganic Biochemistry | 2008
Heveline Silva; Carolina V. Barra; Cristiane F. da Costa; Mauro V. de Almeida; Eloi T. Cesar; Josianne Nicácio Silveira; Arlette Garnier-Suillerot; Flávia C.S. de Paula; Elene C. Pereira-Maia; Ana Paula Soares Fontes
This work describes the synthesis and characterization of four new ligands derived from 1,3-propanediamine in addition to the preparation and characterization of their respective platinum(II) complexes by reaction with K(2)PtCl(4). These ligands were obtained by the reaction of the corresponding alkyl mesylate with 1,3-propanediamine. We have prepared compounds having different carbon chains lengths in an attempt to correlate this factor, which influences the lipophilicity of the compounds, with cytotoxic activity. Octanol/water partition coefficients, the effect of the four complexes on the growth of two tumoral cell lines, and their cellular uptake were investigated. Increasing lipophilicity enhances the rate of cellular uptake and, consequently, the cytotoxic activity.
Journal of the Brazilian Chemical Society | 2006
Wendell Guerra; Iara R. Silva; Elaine de Andrade Azevedo; S. Monteiro; Edmar Chartone-Souza; Josianne Nicácio Silveira; Ana Paula Soares Fontes; Elene C. Pereira-Maia
Este artigo descreve a sintese e a caracterizacao de tres novos complexos de platina(II) com a oxitetraciclina, doxiciclina e clortetraciclina por analise elementar, espectroscopias IV e RMN de 195Pt. As interacoes da doxiciclina com ions PtII em funcao do pH foram estudadas por RMN de 1H. Todas as tetraciclinas investigadas formam complexos 1:1 com a PtII via oxigenio do grupo hidroxila e oxigenio do grupo amida do anel A. As concentracoes minimas inibitorias (MIC) dos ligantes e de seus complexos de PtII foram determinadas em duas cepas sensiveis (E. coli HB 101 and E. coli ATCC 25922) e em uma resistente (E. coli HB101/pBR322). O complexo de platina da doxiciclina e duas vezes mais potente do que o antibiotico livre na cepa resistente. Os coeficientes de particao dos complexos em octanol e agua foram determinados. O aumento da lipofilia causa um aumento da atividade antimicrobiana na cepa resistente.
Journal of the Brazilian Chemical Society | 2006
Nicolás A. Rey; B. C. Menezes; Antonio S. Mangrich; Elene C. Pereira-Maia
Three new copper(II) complexes with the ligands quinuclidine [Cu(C7H13N)2(OH2)Cl]Cl·2H 2O (1), quinine [Cu(C20H23O2N2)(OH 2)2]ClO4 (2), and hydroquinidine [Cu(C20H27O2N2)(OH 2) Cl2]Cl·½H2O (3) have been isolated and characterized. The binding sites were assigned on the basis of vibrational spectroscopy, electron paramagnetic resonance, and thermal analysis results. The possibility of the involvement of the quinuclidinic nitrogen in the coordination was evidenced in complex 1, in which copper(II) is coordinated to two quinuclidine molecules. In the case of quinine-type ligands, if the starting material is deprotonated in both nitrogens, copper(II) coordination occurs through the quinuclidinic nitrogen, as in complex 2. In contrast, if the starting material is protonated in the quinuclidinic nitrogen the binding site is the quinolinic nitrogen, as in complex 3. Therefore, both nitrogens of quinine-type ligands constitute binding sites for copper(II) ions.