Harnessing Brazilian biodiversity database: identification of flavonoids as potential inhibitors of SARS-CoV-2 main protease using computational approaches and all-atom molecular dynamics simulation.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the etiological agent responsible for the global outbreak of COVID-19 (Coronavirus Disease 2019). The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a vital role in mediating viral replication and transcription. In this study, a comprehensive computational approach was employed to investigate the binding affinity, selectivity, and stability of natural product candidates as potential new antivirals acting on the viral polyprotein processing mediated by SARS-CoV-2 Mpro. A library of 288 flavonoids extracted from Brazilian biodiversity was screened to select potential Mpro inhibitors. An initial filter based on Lipinski's rule of five was applied, and 204 compounds that did not violate any of the Lipinski rules were selected. The compounds were then docked into the active site of Mpro using the GOLD program, and the poses were subsequently re-scored using MM-GBSA (Molecular Mechanics Generalized Born Surface Area) binding free energy calculations performed by AmberTools23. The top five flavonoids with the best MM-GBSA binding free energy values were selected for analysis of their interactions with the active site residues of the protein. Next, we conducted a toxicity and drug-likeness analysis, and non-toxic compounds were subjected to molecular dynamics simulation and free energy calculation using the MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method. It was observed that the five selected flavonoids had lower MM-GBSA binding free energy with Mpro than the co-crystal ligand. Furthermore, these compounds also formed hydrogen bonds with two important residues, Cys145 and Glu166, in the active site of Mpro. Two compounds that passed the drug-likeness filter showed stable conformations during the molecular dynamics simulations. Among these, NuBBE_867 exhibited the best MM-PBSA binding free energy value compared to the crystallographic inhibitor. Therefore, this study suggests that NuBBE_867 could be a potential inhibitor against the main protease of SARS-CoV-2 and may be further examined to confirm our results.

Exploring Natural Alkaloids from Brazilian Biodiversity as Potential Inhibitors of the Aedes aegypti Juvenile Hormone Enzyme: A Computational Approach for Vector Mosquito Control.

This study explores the potential inhibitory activity of alkaloids, a class of natural compounds isolated from Brazilian biodiversity, against the mJHBP enzyme of the Aedes aegypti mosquito. This mosquito is a significant vector of diseases such as dengue, zika, and chikungunya. The interactions between the ligands and the enzyme at the molecular level were evaluated using computational techniques such as molecular docking, molecular dynamics (MD), and molecular mechanics with generalized Born surface area (MMGBSA) free energy calculation. The findings suggest that these compounds exhibit a high binding affinity with the enzyme, as confirmed by the binding free energies obtained in the simulation. Furthermore, the specific enzyme residues that contribute the most to the stability of the complex with the compounds were identified: specifically, Tyr33, Trp53, Tyr64, and Tyr129. Notably, Tyr129 residues were previously identified as crucial in the enzyme inhibition process. This observation underscores the significance of the research findings and the potential of the evaluated compounds as natural insecticides against Aedes aegypti mosquitoes. These results could stimulate the development of new vector control agents that are more efficient and environmentally friendly.

Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa).

A polysaccharide was isolated from the exudate of a buriti tree trunk (Mauritia flexuosa). The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. In the temperature range of 255-290 °C, the energy involved in the BG degradation process was approximately 17 J/g. DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition.

Spectroscopic methods and in silico analyses using density functional theory to characterize and identify piperine alkaloid crystals isolated from pepper (Piper Nigrum L.).

Communicated by Ramaswamy H. Sarma.

Chemical profile of Lippia thymoides, evaluation of the acetylcholinesterase inhibitory activity of its essential oil, and molecular docking and molecular dynamics simulations.

The essential oils of the fresh and dry flowers, leaves, branches, and roots of Lippia thymoides were obtained by hydrodistillation and analyzed using gas chromatography (GC) and GC-mass spectrometry (MS). The acetylcholinesterase inhibitory activity of the essential oil of fresh leaves was investigated on silica gel plates. The interactions of the key compounds with acetylcholinesterase were simulated by molecular docking and molecular dynamics studies. In total, 75 compounds were identified, and oxygenated monoterpenes were the dominant components of all the plant parts, ranging from 19.48% to 84.99%. In the roots, the main compounds were saturated and unsaturated fatty acids, having contents varying from 39.5% to 32.17%, respectively. In the evaluation of the anticholinesterase activity, the essential oils (detection limit (DL) = 0.1 ng/spot) were found to be about ten times less active than that of physostigmine (DL = 0.01ng/spot), whereas thymol and thymol acetate presented DL values each of 0.01 ng/spot, equivalent to that of the positive control. Based on the docking and molecular dynamics studies, thymol and thymol acetate interact with the catalytic residues Ser203 and His447 of the active site of acetylcholinesterase. The binding free energies (ΔGbind) for these ligands were -18.49 and -26.88 kcal/mol, demonstrating that the ligands are able to interact with the protein and inhibit their catalytic activity.

H3PO4-activated carbons produced from açai stones and Brazil nut shells: removal of basic blue 26 dye from aqueous solutions by adsorption.

The adsorption characteristics of C.I. basic blue 26 (BB26) from aqueous solutions onto H3PO4-activated carbons (ACs) produced from açai stones (Euterpe oleracea Martius) and Brazil nut shells (Bertholletia excelsa H. B. K) were investigated in a batch system. The ACs were characterized by XRD, FT-IR, N2 adsorption at 77 K, mercury porosimetry, and acidity/basicity analysis. The pseudo-first-order, pseudo-second-order kinetic models and intraparticle diffusion model were used for the kinetic interpretations. The adsorption processes follow the pseudo-second-order kinetic model. The Boyd plots revealed that the adsorption processes were mainly controlled by film diffusion. Equilibrium data were analyzed by the Langmuir and Freundlich models, at different temperatures. The equilibrium data were best represented by the Langmuir isotherm. The adsorption processes were found to be favorable, exothermic, and spontaneous. The açai stones and Brazil nut shells-based ACs were shown to be effective adsorbents for removal of BB26 from aqueous solutions.

An In Silico Study of the Antioxidant Ability for Two Caffeine Analogs Using Molecular Docking and Quantum Chemical Methods.

The antioxidant activity of molecules constitutes an important factor for the regulation of redox homeostasis and reduction of the oxidative stress. Cells affected by oxidative stress can undergo genetic alteration, causing structural changes and promoting the onset of chronic diseases, such as cancer. We have performed an in silico study to evaluate the antioxidant potential of two molecules of the zinc database: ZINC08706191 (Z91) and ZINC08992920 (Z20). Molecular docking, quantum chemical calculations (HF/6-31G**) and Pearson's correlation have been performed. Molecular docking results of Z91 and Z20 showed both the lower binding affinity (BA) and inhibition constant (Ki) values for the receptor-ligand interactions in the three tested enzymes (cytochrome P450-CP450, myeloperoxidase-MP and NADPH oxidase-NO) than the control molecules (5-fluorouracil-FLU, melatonin-MEL and dextromethorphan-DEX, for each receptor respectively). Molecular descriptors were correlated with Ki and strong correlations were observed for the CP450, MP and NO receptors. These and other results attest the significant antioxidant ability of Z91 and Z20, that may be indicated for further analyses in relation to the control of oxidative stress and as possible antioxidant agents to be used in the pharmaceutical industry.

Study of molecular interactions between Chitosan and Vi Antigen.

Chitosan has attracted much interest due to its special physical and chemical properties related to drug administration. Nanoparticles delivery systems from Vi Antigen are a promising approach in the struggle against typhoid fever. In this paper, we reported the obtainment and the characterization of Vi Antigen by Infrared spectroscopy as well as Molecular Modeling and Computational Chemistry studies of the Chitosan-Vi Antigen interaction through theoretical models. The results of the theoretical and experimental Infrared spectroscopy showed important bands related to N-Acetyl and O-Acetyl groups present in Vi Antigen. Important interactions related to its adsorption were observed through three-dimensional optimized structures. Two models were proposed for the Chitosan-Vi Antigen in adsorption system, one as a monomer and another as an optimized tetrasaccharide antigen. The Molecular Modeling studies presented the best conformation and binding site on the nanoparticle Chitosan-Vi Antigen in models proposed. Interactions were observed between O-Acetyl and N-Acetyl groups the Vi Antigen and hydroxy, amino and methyl groups the Chitosan.

Biological activities of Croton palanostigma Klotzsch.

BACKGROUND: Different species of Croton are used in traditional Amazonian medicine. Among the popular uses are treatment of bacterial diseases, poorly healing wounds and fevers. OBJECTIVE: This study evaluated the antileishmanial, antiplasmodial and antimicrobial activities of the extracts and diterpenes of Croton palanostigma Klotzsch (Euphorbiaceae). MATERIALS AND METHODS: Leaves and bark were extracted with dichloromethane and methanol. The bark dichloromethane extract (BDE) was chromatographed on a column, obtaining cordatin and aparisthman. The extracts and diterpenes were assayed thought agar disk diffusion method and their bactericidal or fungicidal effects were evaluated by minimum bactericidal or fungicidal concentration. The antiplasmodial activity was evaluated after 24 and 72 h of exposition. The antileishmanial activity was performed on promastigotes forms of Leishmania amazonensis. RESULTS: The bark methanol extract (BME) and cordatin were not active against any microbial strains tested; BDE and leaves methanol extract (LME) were positive for Pseudomonas aeruginosa and aparisthman was positive for Candida albicans. In the determination of the minimum bactericidal concentration, neither of them were active in the highest concentration tested. The extracts and diterpenes were inactive in Plasmodium falciparum, except the LME in 72 h. Any extract was shown to be active in promastigote forms of L. amazonensis. CONCLUSION: These results indicate that the BDE and LME did not inhibit the bacterial growth, then they probably had bacteriostatic effect. LME presented activity in P. falciparum.

Production and characterization of absorbent heat from the bark of residual Brazil nut bark (Bertholletia Excelsa l.).

BACKGROUND: The increasing efforts to reduce the environmental impact on the Amazon's natural resources are focusing on watercourses that pass through effluents with high concentrations of heavy metals. The adsorption by absorbent is one of the methods used to remove metallic ions. In this assignment, the preparation of activated carbon from Brazil nut bark (Bertholletia excelsa l.), which is a waste material produced from the use of seeds in foodstuffs and cosmetics, is shown. RESULTS: The absorbent was carbonized at 400 °C in 3 h and activated at 800 °C in 2 h, having received the name of AC2, and, the specific area, pore size, real and apparent densities, porosity, scanning electron microscopy (SEM) coupled to energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), pH, moisture, fixed carbon and surface functional groups by Boehm method and Fourier transformed infrared spectroscopy (FTIR) were characterized. According to the results, the carbon presented alkaline characteristic, mesoporosity, average pore diameters of 2.203 nm and specific surface area by BET of 464.835 m(2) g(-1). The efficiency of removal was performed in synthetic solutions of copper sulphate (II) pentahydrate (CuSO4.5H2O), evaluating the influence of pH, initial concentration of copper solution (II), particle diameter and time contact of the adsorbent in solution. The results of higher removal percentages were to pH 5.09, initial concentration of 50, 100 and 150 mg(-1) diameter 0.595 < D < 1.19 mm and time contact of 5 min. CONCLUSIONS: The Brazil nut bark is shown to be an important bio-waste, being an excellent alternative material for the low-cost production of activated carbon for use in processes involving iterations of adsorption.

Rational Design of Antimalarial Drugs Using Molecular Modeling and Statistical Analysis.

Artemisinin is an antimalarial compound isolated from Artemisia annua L. that is effective against Plasmodium falciparum. This paper proposes the development of new antimalarial derivatives of artemisinin from a SAR study and statistical analysis by multiple linear regression (MLR). The HF/6-31G** method was used to determine the molecular properties of artemisinin and 10 derivatives with antimalarial action. MEP maps and molecular docking were used to study the interface between ligand and receptor (heme). The Pearson correlation was used to choose the most important properties interrelated to the antimalarial activity: Hydration Energy (HE), Energy of the Complex (Ecplex), bond length (FeO1), and maximum index of R/Electronegativity of Sanderson (RTe+). After the Pearson correlation, 72 MLR models were built between antimalarial activity and molecular properties; the statistical quality of the models was evaluated by means of correlation coefficient (r), squared correlation coefficient (r(2)), explained variance (adjusted R(2)), standard error of estimate (SEE), and variance ratio (F), and only four models showed predictive ability. The selected models were used to predict the antimalarial activity of ten new artemisinin derivatives (test set) with unknown activity, and only eight of these compounds were predicted to be more potent than artemisinin, and were therefore subjected to theoretical studies of pharmacokinetic and toxicological properties. The test set showed satisfactory results for six new artemisinin compounds which is a promising factor for future synthesis and biological assays.

Análise microbiológica de molhos de pimenta (tucupi com pimenta) comercializados em redes de supermercados e feiras livres na cidade de Belém, PA / Microbiological analysis of pepper sauces (pepper tucupi) sold in supermarkets and street in Belém, PA

A comercialização de alimentos em feiras livres é de grande preocupação para vigilância sanitária, já que é difícil haver o controle de produção até a distribuição, isso faz com que alguns consumidores façam opção por comprarem produtos em supermercados, confiando que nestes existe uma fiscalização mais eficaz, onde os seus produtos são mais seguros. Nesse contexto avaliaram-se as condições microbiológicas de amostras de molho de pimenta (tucupi com pimenta) coletadas em duas grandes redes de supermercados e duas grandes feiras livres do município de Belém do Pará.(...)