Kelson M T Oliveira
Universidade Federal do Amazonas, Química, Faculty Member
Abstract Bergenin is a polyphenol found in many medicinal plants that presents numerous activities, such as antiulcer, anti-inflammatory, antifungal, anticancer, antimicrobial, antidiabetic, antiviral and antioxidant, being, therefore, a... more
Abstract Bergenin is a polyphenol found in many medicinal plants that presents numerous activities, such as antiulcer, anti-inflammatory, antifungal, anticancer, antimicrobial, antidiabetic, antiviral and antioxidant, being, therefore, a research target nowadays. In the present study, bergenin, isolated from Endopleura uchi Huber Cuatrecasas plant, was studied through density functional theory (DFT) and time-dependent density functional theory (TD-DFT), at the B3LYP/6–311++G(2d,2p) and B3LYP-D3(BJ)/6–311+G(2d,p) levels, where the obtained optimized geometry, FT-IR and UV–Vis data were analyzed along with experimental data. The comparative IR studies, together with potential energy distribution (PED) calculation, enabled the assignment of the observed experimental IR bands, besides evaluating the existence of intermolecular H-bonds through dimers formation. The calculated electronic transitions are in good agreement with the experimental data, which allowed the characterization of the UV–Vis bands. HOMO-LUMO energy gaps, average local ionization energy (ALIE) surfaces and Fukui indices calculations were carried out, allowing to concisely evaluate the reactive sites of bergenin. Also, calculations of solvation free energies and free energies of association in water, methanol and ethanol were performed. Due to the know in vitro anti-inflammatory and anticancer activities presented by bergenin, molecular docking and molecular dynamic (MD) calculations were carried out in front of cyclooxygenases 1 and 2 and topoisomerases I and II, revealing good interactions of bergenin with the active site of the tested enzymes, justifying the experimental results found in literature.
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Abstract The high incidence of dengue, chikungunya, and Zika indicates the importance of controlling the vector of these arboviruses in the tropical and subtropical regions of the world. However, vector control is hindered by pesticide... more
Abstract The high incidence of dengue, chikungunya, and Zika indicates the importance of controlling the vector of these arboviruses in the tropical and subtropical regions of the world. However, vector control is hindered by pesticide resistance and the limited success of biocontrol programs against Aedes mosquitoes. Despite these difficulties, the study of common plant species, including those with commercial value, can offer effective and ecological tools in the fight against mosquitoes. In the present study, the essential oils obtained from the aerial parts of Origanum vulgare L. and Thymus vulgaris L. were analyzed by GC–MS and evaluated for their larvicidal, adulticidal and repellent activities against Aedes aegypti L. The main constituents of the O. vulgare essential oil were terpinen-4-ol (17.4%), carvacrol (16.0%) and thymol (10.4%), and the main constituents of the T. vulgaris essential oil were thymol (40.0%), p-cymene (19.3%) and γ-terpinene (17.3%). Both essential oils were toxic to Ae. aegypti larvae with LC50 values of 37.5 μg/mL for O. vulgare and 38.9 μg/mL for T. vulgaris. For adult mosquitoes, the LC50 values were 14.3 and 11.7 μg/mL, respectively. The essential oils of O. vulgare and T. vulgaris showed a significant repellency effect, with values ranging from 8.9% to 37.8% and 4.4% to 68.9%, respectively. In addition, morphological differences between larvae treated with the EOs and the control group were evidenced by optical microscopy. Thus, the results suggest that the essential oils of O. vulgare and T. vulgaris have potential use as an ecofriendly source to develop new insecticides for the control of Ae. aegypti.
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ABSTRACT In this study, guadiscine (G1) and guadiscidine (G2), 7,7-dimethylaporphine alkaloids from Guatteria plants, have they geometric paramaters, vibrational behavior and quantum chemical properties (HOMO-LUMO, MEP, ALIE and Fukui... more
ABSTRACT In this study, guadiscine (G1) and guadiscidine (G2), 7,7-dimethylaporphine alkaloids from Guatteria plants, have they geometric paramaters, vibrational behavior and quantum chemical properties (HOMO-LUMO, MEP, ALIE and Fukui indices) analyzed through a theoretical view, by density functional theory (DFT), using the Becker's three-parameter hybrid exchange functional combined with the Lee–Yang–Parr correlation functional (B3LYP) and 6-311G(2d,p) and 6-311G++(2df,3p) basis set. The obtained geometry data were compared with x-ray data for (−)-N-acetyl-anonaine showing close values. Vibrational analysis, together with potential energy distribution (PED) calculations, revealed several characteristic vibrations that characterize the 7,7 dimethylaporphine skeleton, besides enabling the observation of intermolecular H-bonds through dimers formation. Molecular dynamic simulations were carried out, allowing to evaluate the solvation free energies of G1 and G2 in water, methanol and ethanol, as well as the H-bonds formation between G1 and G2 and the tested solvents. The antineoplastic potential of the title molecules was evaluated via molecular docking calculations with topoisomerase I complexed with DNA. Guadiscine and guadiscidine showed, respectively, free binding energies of -8.0 and -8.5 kcal/mol, while topotecan, a DNA topoisomerase I inhibitor, showed a binding free energy value of -12 kcal/mol, indicating that the studied molecules are good topoisomerase I inhibitors. In vitro cytotoxicity assay with HepG2 cell line were performed, revealing significant antitumor potential of the studied molecules.
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According to the World Health Organisation, on March 27, 2020, the number of confirmed cases of COVID-19 has already exceeded 509.000 with about of 23.000 deaths worldwide. Given this, the impact of COVID-19 on humanity cannot be... more
According to the World Health Organisation, on March 27, 2020, the number of confirmed cases of COVID-19 has already exceeded 509.000 with about of 23.000 deaths worldwide. Given this, the impact of COVID-19 on humanity cannot be overlooked, and basic research are urgently needed. This research aims to find antagonists already approved for another diseases, that may inhibit activity of the main protease (Mpro) of the SARS-CoV-2 virus, as well as modulate the ACE2 receptors, largely found in lung cells and reduce viral replication by inhibiting NSP12 RNA Polymerase. Docking molecular simulations were realized among a total of 28 ligands published in the literature against COVID-19. Docking studies were made with algorithm of AutoDock Vina 1.1.2 software. A structure-based virtual screening was performed with MTiOpenScreen. Subsequently, the physical-chemical and pharmacokinetic parameters were analyzed with SwissADME in order to select only the most promising ones. Finally, simulatio...
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The goal of this study is to select electronic properties (variables or descriptors) responsible for peroxynitrite scavenging ability of a set of 24 flavonoids. To do so, electronic parameters were calculated by using DFT and chemometric... more
The goal of this study is to select electronic properties (variables or descriptors) responsible for peroxynitrite scavenging ability of a set of 24 flavonoids. To do so, electronic parameters were calculated by using DFT and chemometric methods (Principal Component Analysis, Hierarchical Cluster Analysis and K-Nearest Neighbor) in order to build models able to establish relationships between electronic features and the
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Phospholipases A2 (PLA2) are enzymes that trigger the degradation cascade of the arachidonic acid, leading to the formation of pro-inflammatory eicosanoids. The selective inhibition of PLA2s is crucial in the search for a more efficient... more
Phospholipases A2 (PLA2) are enzymes that trigger the degradation cascade of the arachidonic acid, leading to the formation of pro-inflammatory eicosanoids. The selective inhibition of PLA2s is crucial in the search for a more efficient anti-inflammatory drug with fewer side effects than the drugs currently used. Hence, we studied the influences caused by two pyrazolonic inhibitors: dipyrone (DIP) and 1-phenyl-3-methyl-5-pyrazolone
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A fast way to reconstruct the three-dimensional molecular conformation of SARS-CoV-2 virus proteins is addressed in this article, involving the most worrying variant discovered in patients from Brazil, the lineage $B$.1.1.28/$P$.1. The... more
A fast way to reconstruct the three-dimensional molecular conformation of SARS-CoV-2 virus proteins is addressed in this article, involving the most worrying variant discovered in patients from Brazil, the lineage $B$.1.1.28/$P$.1. The proposed methodology is based on the sequencing of virus proteins and that, through the incorporation of mutations in silico, which are then computationally reconstructed using an enumerative feasibility algorithm validated by the Ramachandran diagram and structural alignment, in addition to the subsequent study of structural stability through classical molecular dynamics. From the resulting structure to the ACE2-RBD complex, the valid solution presented 97.06% of the residues in the most favorable region while the reference crystallographic structure presented 95.0%, a difference therefore very small and revealing the great consistency of the developed algorithm. Another important result was the low RMSD alignment between the best solution by the BP algorithm and the reference structure, where we obtained 0.483Å. Finally, the molecular dynamics indicated greater structural stability in the ACE2-RBD interaction with the P.1 strain, which could be a plausible explanation for convergent evolution that provides an increase in the interaction affinity with the ACE2 receptor.
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All molecular dynamics simulations were performed in GROMACS 2019.1 software by Prof. Dr. Jonathas N. Silva. The time interval for each simulation is 50ns. Among the crystallographic structures, we have the antibody-antigen complex... more
All molecular dynamics simulations were performed in GROMACS 2019.1 software by Prof. Dr. Jonathas N. Silva. The time interval for each simulation is 50ns. Among the crystallographic structures, we have the antibody-antigen complex containing the P.1 variant (PDB ID: 7NXB), and the respective wild-type structure (PDB ID: 7NX6) In preparing the topology, Na+ and Cl- ions were inserted to neutralize the system at a concentration of 0.15 mol/L. Trajectory files were simulated based on the CHARMM36 force field. We use a cubic solvation box, by the TIP3P water model. The production of trajectories was carried out using the NPT canonical cycle. The Parrinello–Rahman barostat was adopted to keep the pressure constant at 1 atm, while the Berendsen algorithm acted as a thermostat to keep the system temperature at 300 K.
ABSTRACTThe new β-coronavirus has been causing sad losses around the world and the emergence of new variants has caused great concern. This pandemic is of a proportion not seen since the Spanish Flu in 1918. Thus, throughout this... more
ABSTRACTThe new β-coronavirus has been causing sad losses around the world and the emergence of new variants has caused great concern. This pandemic is of a proportion not seen since the Spanish Flu in 1918. Thus, throughout this research, the B.1.1.28 lineage of the P.1 clade (K417T, N501Y, E484K) that emerged in Brazil was studied, as well as the latest Delta variant. This is because the molecular mechanisms by which phenotypic changes in transmissibility or mortality remain unknown. Through molecular dynamics simulations with the NAMD 3 algorithm in the 50ns interval, it was possible to understand the impact on structural stabilization on the interaction of the ACE2-RBD complex, as well as simulations in 30ns for the neutralizing antibody P2B-2F6, with this antibody was derived from immune cells from patients infected with SARS-CoV-2. Although not all molecular dynamics analyzes support the hypothesis of greater stability in the face of mutations, there was a predominance of low ...
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The novel β-coronavirus has caused sad losses worldwide and the emergence of new variants has been causing great concern. Thus throughout this research the lineage B.1.1.28 of clade P.1 (K417T, N501Y, E484K) that emerged in Brazil was... more
The novel β-coronavirus has caused sad losses worldwide and the emergence of new variants has been causing great concern. Thus throughout this research the lineage B.1.1.28 of clade P.1 (K417T, N501Y, E484K) that emerged in Brazil was studied but also in a less depth the P.2 lineage, where through simulations of molecular dynamics in the NAMD 3 algorithm in the 18 ns interval it was possible to understand the thermodynamic impacts in the interaction of the ACE2-RBD complex and the neutralizing antibody RBD-IgG. From the molecular dynamics, we noticed that the RMSF averages in the P.1 strain were more expressive in comparison to the ACE2-RBD wild-type and consequently some regions have undergone more expressive conformational changes although, in general, a greater stabilization of the complex was perceived. In addition, was an increase in the average number of Hydrogen bonds generating a lower RMSD and greater system compaction measured by Radius of Gyration (Rg). The change in nati...
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4-Nerolidylcatechol (4NRC), a secondary metabolite described as a potent antioxidant that presents anti-inflammatory, antimalarial, analgesic, and cytotoxic properties, has been receiving prominence in the catechol class. In this work, a... more
4-Nerolidylcatechol (4NRC), a secondary metabolite described as a potent antioxidant that presents anti-inflammatory, antimalarial, analgesic, and cytotoxic properties, has been receiving prominence in the catechol class. In this work, a theoretical DFT study of the vibrational, structural, and quantum properties of 4-nerolidylcatechol (4NRC) using the B3LYP/6-311G (2d,p) level is presented. The theoretical molecular geometry data were compared with the X-ray data of a similar molecule in the associated literature and a conformational study is presented, with the aim of providing a good comprehension of the 4NRC structural arrangement and stability. Also, HOMO-LUMO energy gap and natural bond orbitals (NBOs) were performed and discussed. The calculated UV spectrum showed similarity to the experimentally obtained data, with transitions assigned. The comparative IR studies revealed that intermolecular hydrogen bonds that stabilize dimeric forms are plausible and also allowed the assig...
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A combined experimental and theoretical DFT study of the structural, vibrational and electronic properties of liriodenine is presented using B3LYP function with 6-311G (2d, p) basis set. The theoretical geometry optimization data were... more
A combined experimental and theoretical DFT study of the structural, vibrational and electronic properties of liriodenine is presented using B3LYP function with 6-311G (2d, p) basis set. The theoretical geometry optimization data were compared with the X-ray data for a similar structure in the associated literature, showing similar values. In addition, natural bond orbitals (NBOs), HOMO-LUMO energy gap, mapped molecular Electrostatic Potential (MEP) surface calculation, first and second order hyperpolarizabilities were also performed with the same calculation level. Theoretical UV spectrum agreed well with the measured experimental data, with transitions assigned. The molecular electrostatic potential map shows opposite potentials regions that forms hydrogen bonds that stabilize the dimeric form, which were confirmed by the close values related to the CO bond stretching between the dimeric form and the experimental IR spectra (1654cm(-1) for the experimental, 1700cm(-1) for the dime...
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A detailed structural analysis and spectral behavior of the glucoalkaloid strictosidine, a precursor of all monoterpene indole alkaloids, are discussed. The experimental NMR, FTIR, and UV results were compared to the theoretical DFT... more
A detailed structural analysis and spectral behavior of the glucoalkaloid strictosidine, a precursor of all monoterpene indole alkaloids, are discussed. The experimental NMR, FTIR, and UV results were compared to the theoretical DFT spectra calculated by Becke using the three-parameter Lee-Yang-Parr (B3LYP) function with 6-31G(d) and 6-311++G(2d,p) basis sets. The theoretical geometry optimization data were compared with the X-ray data for precursors and similar structures in the associated literature. The similarity between the theoretical and experimental coupling constants values made it possible to affirm the values of dihedral angles and their configuration, reinforcing findings from previous stereochemical studies. Theoretical UV analysis agreed well with the measured experimental data, with bands assigned. Calculated HOMO/LUMO gaps show low excitation energy for strictosidine, justifying its stability and reaction kinetics. The molecular electrostatic potential map shows opposite potentials regions that form hydrogen bonds that stabilize the dimeric form, which were confirmed by excellent agreement of the dimeric form theoretical wavenumbers with the experimental IR spectrum. ESI-MS/MS data revealed patterns for the fragmentation of the protonated strictosidine molecule outlined by an NBO study.
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In recent years, theoretical and experimental studies have presented efforts to understand the origin of the building blocks that gave rise to life, generating a lot of discussion about abiogenesis theme. The most widely widespread... more
In recent years, theoretical and experimental studies have presented efforts to understand the origin of the building blocks that gave rise to life, generating a lot of discussion about abiogenesis theme. The most widely widespread idea maintains that life arose spontaneously through five main stages: (1) prebiotic synthesis of nucleotides; (2) prebiotic formation of polynucleotides from the nucleotides; (3) emergence of special RNA molecules catalyzing their own replication; (4) evolution of the primordial replicases towards more efficient ones; (5) emergence and evolution of other and better catalytic RNA molecules. All stages are target of much speculation and discussion as original conditions cannot be replicated faithfully in the laboratory, and there is no guarantee that it will be performed in the future. This work, from a semi-empirical theoretical approach, investigates some aspects of the two first stages by means of thermochemical data from the prebiotic nucleotide synthesis reactions, and short sequences of DNA and RNA. The objective was to verify that various abiotic reactions identified in the literature as natural precursor in the formation of life blocks can occur spontaneously in abiotic environment. Gibbs free energy was used as calculating criterion , since the thermodynamic parameters calculated by semi-empirical methods such as AM1 and PM3 has shown a good correlation with experimental data.