Elaine F. F. da Cunha

Centro Universitário de Lavras, لفراس, Minas Gerais, Brazil

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Publications (93)159.56 Total impact

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    ABSTRACT: A series of novel isocoumarin derivatives were synthesized using Castro–Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different tumor cells. Furthermore, docking calculations were performed for the kallikrein 5 (KLK5) active site to predict the possible mechanism of action of this series of compounds. Theoretical findings indicate that the 3,4-dihydroisocoumarin derivative 10a forms hydrogen bonds with Ser190 and Gln192 residues of KLK5. This derivative was the most active compound in the series with potent antiproliferative activity and high selectivity index (SI > 378.79) against breast cancer cells (MCF-7, GI50 = 0.66 μg mL-1). This compound represents a promising matrix for developing new antiproliferative agents.
    No preview · Article · Jan 2016 · European Journal of Medicinal Chemistry
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    ABSTRACT: In the present study, quantitative structure-activity relationship studies which make use of molecular dynamics trajectories were performed on a set of 54 glucokinase protein activators. The conformations obtained by molecular dynamics simulation were superimposed according to the twelve alignments tested in a virtual three-dimensional box comprised of 2Å cells. The models were generated by the technique that combines genetic algorithms (GA) and partial least squares (PLS). The best alignment models generated with a determination coefficient (r(2) ) between 0.674 and 0.743 and cross-validation (q(2) ) between 0.509 and 0.610, indicating good predictive capacity. The 4D-QSAR models developed in this study suggest novel molecular regions to be explored in the search for better glucokinase activators. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Chemical Biology & Drug Design
  • Estella G. da Mota · Elaine F. F. da Cunha · Matheus P. Freitas
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    ABSTRACT: This work reports the docking studies of compounds designed from the combination of substructures of three types of antihypertensives: angiotensin converting- enzyme (ACE) inhibitors, calcium channel blockers and renin inhibitors. Consequently, multi-target compounds are expected to be obtained. Indeed, a few purposes showed both docking scores and intermolecular ligand-enzyme interaction towards all three targets higher than the reference compounds Captopril (ACE inhibitor), Amlodipine (calcium channel blocker) and Aliskiren (renin inhibitor). Particularly, the proposed compound 18 (containing a phenyl group, a substituted dihydropyridine and a piperazinyl-like group as substituents at the indoline scaffold) is a promising ligand for all three enzymatic targets. These results, which were discussed in terms of ligand-enzyme interactions (especially hydrogen bonding between amino acid residues and ligands), indicate promising perspectives for synthesis and biological tests.
    No preview · Article · Nov 2015 · Letters in Drug Design & Discovery
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    ABSTRACT: Chitosan is a polymer with interesting characteristics for use in catalysis, such as biocompatibility, high chemical reactivity and stability under various conditions. Seeking new applications, a new hybrid material was synthesized for use in the degradation of organic compound. A synthesis route proposed led to the formation of a material in the form of film. The characterization data indicated the presence of hematite, as well as metallic iron. In addition, a theoretical model for interaction of iron with chitosan was proposed. Molecular dynamics simulations indicate that non-Coulomb interactions modulate the adsorption process between reactive red dye and chitosan. The catalytic behavior of these hybrid materials was investigated for the H2O2 decomposition to O2 and the degradation of reactive red dye. The hybrid material showed high degradation capacity, confirming this material as an efficient heterogeneous Fenton catalysts.
    Full-text · Article · Oct 2015 · Journal of the Iranian Chemical Society

  • No preview · Article · Sep 2015 · Letters in Drug Design & Discovery
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    ABSTRACT: The 4-hydroxyphenylpyruvate dioxygenase (HPPD) is a relevant target protein for therapeutic and agrochemical research. It is an iron-dependent enzyme, and its inhibition has very different effects on plants and animals. In animals, the enzyme has an important role in the catabolism of tyrosine, and in the plant, it operates in the cascade of photosynthesis. Potent HPPD inhibitors have been described, and all contain the 1,3-diketone group in its shape. In this research, we carried out a study of the interaction modes of HPPD enzymes from plant and rat with selective and non-selective herbicides which already available with their structures to identify the molecule groups which are essential to their activity and those that are likely to changes, mediated by molecular computations. In this theoretical investigation, methods of molecular docking, reaction mechanism (QM/MM) and AIM calculations were employed, aiming the search for new more active and selective herbicides. Modifications were performed for DAS 645 and DAS 869 inhibitors. DAS 645 presented a good selectivity for the inhibition of the plant enzyme, and the modifications to the analogs design done increased its activity. For this compound, π-π∗stacking interactions seem to be important, and this fact was proven by using AIM calculations. The other prototype compound, DAS 869, a potent inhibitor for both enzymes, had its increased activity in the plant and rat enzyme after added groups capable of performing π-π∗stacking interactions.
    Full-text · Article · Aug 2015 · Medicinal Chemistry Research
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    ABSTRACT: Bruton's tyrosine kinase (Btk) is an important enzyme in B-lymphocyte development and differentiation. Furthermore, Btk expression is considered essential for the proliferation and survival of these cells. Btk inhibition has become an attractive strategy for treating autoimmune diseases, B-cell leukemia and lymphomas. With the objective of proposing new candidates for Btk inhibitors, we applied receptor-dependent four-dimensional quantitative structure-activity relationship methodology to a series of ninety-six nicotinamide analogs useful as Btk modulators. The QSAR models were developed using seventy-one compounds, the training set, and externally validated using twenty-five compounds, the test set. The conformations obtained by molecular dynamics simulation were overlapped in a virtual three dimensional cubic box comprised of 2 and 5Å cells, according to the six trial alignments. The models were generated by combining genetic function approximation (GFA) and partial least squares (PLS) regression technique. The analyses suggest that Model 1a yields the best results. The best equation shows q(2)adjusted = 0.638, r(2) = 0.743, RMSEC = 0.831, RMSECV = 0.879. Given the importance of the Tyr551, this residue could become a strategic target for the design of novel Btk inhibitors with improved potency. In addition, the good potency predicted for the proposed M2 compound indicates this compound as a potential Btk inhibitor candidate.
    No preview · Article · Aug 2015 · Journal of biomolecular Structure & Dynamics
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    ABSTRACT: Cancer is a global epidemic, which significantly affects all ages and socio-economic groups and one reason is the great difficulty of the initial diagnostic phase. The Magnetic Resonance Imaging (MRI), through effective contrast agents, has greatly helped in the diagnosis at the initial stage. Recently, superparamagnetic iron oxide nanoparticles and complexes with Mn2+ have received great attention due to their applications as contrast agents for Magnetic Resonance Imaging (MRI). Those materials can shorten the T2 and T2∗ transverse relaxation times. Thus, in this work, the face 100 of the δ-FeOOH and the complex [MnH3buea(OH)]2− were studied with explicit water molecules in order to obtain the 1H and 17O hyperfine coupling constants (HFCCs). Molecular dynamics (MD) simulations were performed using the ReaxFF program for subsequent statistical inefficiency calculations. Thus, the structures from the MD simulation were selected for HFCC calculations. The theoretical results suggest that the δ-FeOOH and [MnH3buea(OH)]2− considerably increase the 1H and 17O hyperfine coupling constants of the water molecules. In addition, δ-FeOOH is sensitive to 1H and 17O HFCCs parameters, however, in the complex [MnH3buea(OH)]2−, 17O is much more sensitive than 1H in relation to the HFCC parameters. Our findings point out δ-FeOOH as a promising alternative to conventional contrast agents.
    Full-text · Article · Aug 2015 · Computational and Theoretical Chemistry
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    ABSTRACT: Water pollution is a significant and growing problem throughout the world, especially in developing countries. In order to minimize environmental problems, catalysts have increasingly been designed to remove pollutants from the water. In an attempt to innovate by the creation of new low-cost alternatives to efficiently remove pollutants, the enzymatic treatment has been intensely studied for this purpose. Reactions catalyzed by enzymes are able to perform specific treatments, commonly with high rates of the final products. With this, the enzyme, peroxidase, is a promising candidate as a bioremediation catalyst. The efficiency of oxidoredutive enzymes, such as horseradish peroxidase (HRP) and soybean peroxidase (SP) have been studied, given that their performance depends on the substrate. In this investigation, experimental techniques and theoretical calculations have been employed in order to investigate the oxidative process for the ferulic acid and bromophenol blue dyes, performed by HRP and SP. Both enzymes showed a comparable behavior with respect to ferulic acid substrate. On the other hand, by utilizing bromophenol blue dye as a substrate, the behavior of the employed catalysts was significantly different. Experimental data have shown that HRP was more active toward bromophenol blue when compared to ferulic acid, being more rapidly degraded by the HRP enzyme. This tendency was confirmed by our theoretical Docking, PM6 semi-empirical method and DFT calculation results, in which the interaction, binding energies and transition states were determined.
    Full-text · Article · Jul 2015 · Journal of biomolecular Structure & Dynamics
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    ABSTRACT: Renin inhibitors pertain to a new generation class of antihypertensive agents. There are only a few studies on the computational modeling of such class of compounds and only one available drug in the market used as renin inhibitor for the treatment of hypertension, aliskiren. The present study reports the QSAR modeling of the activities of a series of indole-3-carboxamide derivatives using MIA-QSAR in order to propose new promising analogs as renin inhibitor candidates. The proposed structures were submitted to docking evaluation to search for the interaction modes responsible for the calculated bioactivities. In addition, the drug likeness of the proposed compounds was investigated using theoretical data related to pharmacokinetic properties. Overall, at least two promising candidates are proposed as highly active and pharmacokinetically acceptable renin inhibitors.
    No preview · Article · Jul 2015 · Medicinal Chemistry Research
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    ABSTRACT: One serious consequence of the current consumer society is the transformation of the environment into a waste receptacle arising from human activities. Because of the potential toxic effects of chromium solid waste containing this metal there are grounds for serious concern for the tanning and leather processing industry. The application of tannery waste as organic fertilizer has led to extensive contamination by chromium in agricultural areas and may cause the accumulation of this metal in soils and plants. This work evaluated the extraction of Cr +3 and Cr +6 contained in solid waste from the leather industry through density functional theory (DFT) calculations. The Gibbs free energy calculations reveal that the chelator ethylenediaminetetraacetic acid (EDTA) forms more stable complexes with metal ions of chromium compared with the structures of the complexes [Cr(NTA)(H 2 O) 2 ] and [Cr-collagen], the latter used to simulate the protein bound chrome leather.
    Full-text · Article · Jan 2015
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    ABSTRACT: Abstract Nerve agents are organophosphates acting as potent inhibitors of acetylcholinesterase (AChE), the enzyme responsible for the hydrolysis of acetylcholine and, consequently, the termination of the transmission of nerve impulses. The inhibition of AChE by an organophosphate can be reversed by a nucleophilic agent able to dephosphorylate a serine residue in the active site of AChE. In this sense, the oximes are compounds capable of removing the nerve agent and reactivate the enzyme. Here we have applied a methodology involving theoretical docking and Quantum Mechanics/Molecular Mechanics (QM/MM), using the softwares Molegro(®) and Spartan(®), to evaluate the kinetic constants of reactivation and the interactions of the oxime BI-6 with AChE inhibited by different organophosphorus compounds (OP) in comparison to in vitro data. Results confirm that this method is suitable for the prediction of kinetic and thermodynamic parameters of oximes, which may be useful in the design and selection of new and more effective oximes.
    Full-text · Article · Nov 2014 · Journal of biomolecular Structure & Dynamics
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    Giovana Baptista Caldas · Teodorico C Ramalho · Elaine F F da Cunha
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    ABSTRACT: Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied to a series of 52 benzothiophene analogs synthesized by Hiroshi Yamashita et al. (2011, United Sates Patent no. US8,349,840) and evaluated as dopamine D2 receptor inhibitors. The QSAR equations, generated by a combined scheme of genetic algorithms (GA) and partial least squares (PLS) regression, were evaluated by leave-one-out cross-validation, using a training and test set of 42 and ten compounds, respectively. Four different alignments were tested, and model 2, generated from Eq. 10, showed the best statistical results; it was therefore chosen to represent the data set. This study allowed a quantitative prediction of compounds potency and supported the design of the new benzothiophene.
    Full-text · Article · Oct 2014 · Journal of Molecular Modeling
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    ABSTRACT: Twelve novel 8-hydroxyquinoline derivatives were synthesized with good yields by performing copper-catalyzed Huisgen 1,3-dipolar cycloaddition ("click" reaction) between an 8-O-alkylated-quinoline containing a terminal alkyne and various aromatic or protected sugar azides. These compounds were evaluated in vitro for their antiproliferative activity on various cancer cell types. Protected sugar derivative 16 was the most active compound in the series, exhibiting potent antiproliferative activity and high selectivity toward ovarian cancer cells (OVCAR-03, GI50 < 0.25 μg mL(-1)); this derivative was more active than the reference drug doxorubicin (OVCAR-03, GI50 = 0.43 μg mL(-1)). In structure-activity relationship (SAR) studies, the physico-chemical parameters of the compounds were evaluated and docking calculations were performed for the α-glucosidase active site to predict the possible mechanism of action of this series of compounds.
    Full-text · Article · Sep 2014 · European Journal of Medicinal Chemistry
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    Dataset: CCHTS 2014

    Full-text · Dataset · Aug 2014
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    ABSTRACT: Magnetite is an iron oxide widely used as contrast agent in MRI, receiving considerable interest from nanoscience and nanotechnology. In this work, the face 1 0 0 of the magnetite structure was studied with water in order to obtain H-1 hyperfine coupling constants (HFCCs). Molecular dynamics (MD) calculations were performed using the ReaxFF program and for statistical inefficiency, structures were selected for HFCC and NMR calculations. From our theoretical findings, the magnetite in solution considerably increases the H-1 HFCC of water molecules. From our results, it is essential to incorporate the dynamics and solvent effects into NMR calculations of relaxation parameters.
    Full-text · Article · Aug 2014 · Chemical Physics Letters
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    ABSTRACT: Leishmania donovani is a parasite that causes visceral leishmaniasis, a severe form of leishmaniasis that affects vital organs. An important target for the treatment of this disease is the protein α - β tubulin, which was modeled in this paper and proposed as a target for the treatment of visceral leishmaniasis. Two classes of compounds were studied, dinitroanilines and oxadiazoles. According to the docking results, dinitroanilines interact better with the L loop domain and oxadiazoles interact better with the colchicine domain.
    Full-text · Article · Jul 2014
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    ABSTRACT: In the present work, we applied docking and molecular dynamics techniques to study 11 compounds inside the enzymes dihydrofolate reductase (DHFR) from the biological warfare agent Bacillus anthracis (BaDHFR) and Homo sapiens sapiens (HssDHFR). Six of these compounds were selected for a study with the mutant BaF96IDHFR. Our results corroborated with experimental data and allowed the proposition of a new molecule with potential activity and better selectivity for BaDHFR.
    Full-text · Article · Jun 2014 · European Journal of Medicinal Chemistry
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    Daniela Rodrigues Silva · Teodorico C. Ramalho · Elaine F. F. da Cunha
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    ABSTRACT: Dopamine is an abundant neurotransmitter in the brain, and acts as a regulator of many physiological functions in the central nervous system, such as motor activity, cognition, and positive reinforcement, and in the periphery, as a modulator of cardiovascular function, among others. Dopamine receptors belong to a superfamily of G protein-coupled receptors, and to date five sequences in the human body have been reported with various isoforms each. Disturbances in the dopaminergic systems are associated with several diseases, such as, for example, Parkinson's disease and schizophre-nia. Since the disturbances affecting the locomotor activity are related to dopamine D 2 receptors. Quantitative structure-activity relationship analysis in four-dimensional (4D-QSAR) studies was applied on a series of 73 tetracyclic tetrahydro-furan derivatives containing a substituted cyclic amine side chain with binding affinity towards dopamine D 2 receptors. The 4D-QSAR models were developed using 60 compounds, the training set, and externally validated using 13 com-pounds, the test set. We tested three different alignments, and the Model 3, generated from Equation 3, showed the best statistical results, the same being chosen to represent the data set. The model developed in this work shows descriptors with important pharmacophoric groups for inhibiting dopamine D 2 receptors, suggesting structural changes for new in-hibitors.
    Full-text · Dataset · May 2014
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    ABSTRACT: Understanding the molecular recognition process of nucleobases is one of the greatest challenges for both computational chemistry and biophysics fields. In fact, our results point out that it is a hard task to take into account the hydrophobic interactions, such as π−π and T-stacking interactions, by theoretical calculations using conven-tional force fields due to quantum effects of hyperconjugation and electronic correlation. In this line, our findings put in evidence that simple modifications in the Lennard-Jones potential can improve theoretical predictions in scenarios where hydrophobic interactions can drive the molecular recognition.
    Full-text · Article · May 2014 · The Journal of Physical Chemistry A

Publication Stats

741 Citations
159.56 Total Impact Points

Institutions

  • 2010-2015
    • Centro Universitário de Lavras
      لفراس, Minas Gerais, Brazil
  • 2007-2015
    • Universidade Federal de Lavras (UFLA)
      • Departamento de Química
      لفراس, Minas Gerais, Brazil
  • 2014
    • Instituto Militar de Engenharia (IME)
      • Secção de Engenharia Química
      Rio de Janeiro, Rio de Janeiro, Brazil
  • 2011-2014
    • Federal University of Minas Gerais
      • Departamento de Química
      Cidade de Minas, Minas Gerais, Brazil
  • 2009
    • Martin Luther University of Halle-Wittenberg
      • Division of Pharmaceutical Chemistry and Clinical Pharmacy
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2005
    • Universidade Aberta do Brasil
      San Paulo, São Paulo, Brazil
  • 2004-2005
    • Federal University of Rio de Janeiro
      • • Departamento de Química Orgânica
      • • Instituto de Química (IQ)
      Rio de Janeiro, Rio de Janeiro, Brazil