Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening.

Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against Ae. aegypti via virtual screening. Pyriproxyfen was chosen as a template compound to search molecules in the database Zinc_Natural_Stock (ZNSt) with structural similarity using ROCS (rapid overlay of chemical structures) and EON (electrostatic similarity) software, and in the final search, the top 100 were selected. Subsequently, in silico pharmacokinetic and toxicological properties were determined resulting in a total of 14 molecules, and these were submitted to the PASS online server for the prediction of biological insecticide and acetylcholinesterase activities, and only two selected molecules followed for the molecular docking study to evaluate the binding free energy and interaction mode. After these procedures were performed, toxicity risk assessment such as LD50 values in mg/kg and toxicity class using the PROTOX online server, were undertaken. Molecule ZINC00001624 presented potential for inhibition for the acetylcholinesterase enzyme (insect and human) with a binding affinity value of -10.5 and -10.3 kcal/mol, respectively. The interaction with the juvenile hormone was -11.4 kcal/mol for the molecule ZINC00001021. Molecules ZINC00001021 and ZINC00001624 had excellent predictions in all the steps of the study and may be indicated as the most promising molecules resulting from the virtual screening of new insecticidal agents.

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.

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.