PESTICIDAS E SEUS RESPECTIVOS RISCOS ASSOCIADOS À CONTAMINAÇÃO DA ÁGUA

Efetuou-se revisão de literatura sobre os principais tipos de pesticidas, bem como suas toxicidades e riscos associados à contaminação da água e do meio ambiente. Os pesticidas podem ser bastante úteis na produção agrícola, especialmente quando o clima favorece o desenvolvimento de pragas. Contudo, o seu uso deve ser corretamente orientado por profissionais da área, respeitando-se a legislação vigente e a saúde da população. Para esses fins, as pesquisas na área de pesticidas vêm caminhando na direção da obtenção de compostos cada vez menos tóxicos para os seres vivos. PESTICIDES AND RESPECTIVE RISKS ASSOCIATED TO WATER CONTAMINATION Abstract Literature revision was made on the main pesticides types, as well as its toxicities and risks associated to the contamination of the water and of the environment. The pesticides can be quite useful in the agricultural production, especially when the climate favors the development of plagues. However, its use should be guided correctly by professionals of the area, being respected the effective legislation and the health of the population. For those ends, the researches in the pesticides area come towards the obtention of less toxic compounds for live beings

An Antioxidant Potential, Quantum-Chemical and Molecular Docking Study of the Major Chemical Constituents Present in the Leaves of Curatella americana Linn

Reactive oxygen species (ROS) are continuously generated in the normal biological systems, primarily by enzymes as xanthine oxidase (XO). The inappropriate scavenging or inhibition of ROS has been considered to be linked with aging, inflammatory disorders, and chronic diseases. Therefore, many plants and their products have been investigated as natural antioxidants for their potential use in preventive medicine. The leaves and bark extracts of Curatella americana Linn. were described in scientific research as anti-inflammatory, vasodilator, anti-ulcerogenic, and hypolipidemic effects. So, the aim of this study was to evaluate the antioxidant potentials of leaf hydroalcoholic extract from C. americana (HECA) through the scavenging DPPH assay and their main chemical constituents, evaluated by the following quantum chemical approaches (DFT B3LYP/6-31G**): Maps of Molecular Electrostatic Potential (MEP), Frontier Orbital’s (HOMO and LUMO) followed by multivariate analysis and molecular docking simulations with the xanthine oxidase enzyme. The hydroalcoholic extract showed significant antioxidant activity by free radical scavenging probably due to the great presence of flavonoids, which were grouped in the PCA and HCA analysis with the standard gallic acid. In the molecular docking study, the compounds studied presented the binding free energy (ΔG) values close each other, due to the similar interactions with amino acids residues at the activity site. The descriptors Gap and softness were important to characterize the molecules with antioxidant potential by capturing oxygen radicals

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

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.Federal University of Amapá, Program in Biotechnology and Biodiversity-Network BIONORTE, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for funding in the publication of this article

PESTICIDAS E SEUS RESPECTIVOS RISCOS ASSOCIADOS À CONTAMINAÇÃO DA ÁGUA

Efetuou-se revisão de literatura sobre os principais tipos de pesticidas, bem como suas toxicidades e riscos associados à contaminação da água e do meio ambiente. Os pesticidas podem ser bastante úteis na produção agrícola, especialmente quando o clima favorece o desenvolvimento de pragas. Contudo, o seu uso deve ser corretamente orientado por profissionais da área, respeitando-se a legislação vigente e a saúde da população. Para esses fins, as pesquisas na área de pesticidas vêm caminhando na direção da obtenção de compostos cada vez menos tóxicos para os seres vivos. PESTICIDES AND RESPECTIVE RISKS ASSOCIATED TO WATER CONTAMINATION Abstract Literature revision was made on the main pesticides types, as well as its toxicities and risks associated to the contamination of the water and of the environment. The pesticides can be quite useful in the agricultural production, especially when the climate favors the development of plagues. However, its use should be guided correctly by professionals of the area, being respected the effective legislation and the health of the population. For those ends, the researches in the pesticides area come towards the obtention of less toxic compounds for live beings

Molecular dynamics, density functional, ADMET predictions, virtual screening, and molecular interaction field studies for identification and evaluation of novel potential CDK2 inhibitors in cancer therapy

In this work, we have used molecular dynamics, density functional theory, virtual screening, ADMET predictions, and molecular interaction field studies to design and propose eight novel potential inhibitors of CDK2. The eight molecules proposed showed interesting structural characteristics that are required for inhibiting the CDK2 activity and show potential as drug candidates for the treatment of cancer. The parameters related to the Rule of Five were calculated, and only one of the molecules violated more than one parameter. One of the proposals and one of the drug-like compounds selected by virtual screening indicated to be promising candidates for CDK2-based cancer therapy

Computer-aided drug design and ADMET predictions for identification and evaluation of novel potential farnesyltransferase inhibitors in cancer therapy

We have used various computational methodologies including molecular dynamics, density functional theory, virtual screening, ADMET predictions and molecular interaction field studies to design and analyze four novel potential inhibitors of farnesyltransferase (FTase). Evaluation of two proposals regarding their drug potential as well as lead compounds have indicated them as novel promising FTase inhibitors, with theoretically interesting pharmacotherapeutic profiles, when Compared to the very active and most cited FTase inhibitors that have activity data reported, which are launched drugs or compounds in clinical tests. One of our two proposals appears to be a more promising drug candidate and FTase inhibitor, but both derivative molecules indicate potentially very good pharmacotherapeutic profiles in comparison with Tipifarnib and Lonafarnib, two reference pharmaceuticals. Two other proposals have been selected with virtual screening approaches and investigated by LIS, which suggest novel and alternatives scaffolds to design future potential FTase inhibitors. Such compounds can be explored as promising molecules to initiate a research protocol in order to discover novel anticancer drug candidates targeting farnesyltransferase, in the fight against cancer. (C) 2009 Elsevier Inc. All rights reserved.CNPqCAPESFAPESPFAPER

VALIDATION OF COMPUTATIONAL METHODS APPLIED IN MOLECULAR MODELING OF CAFFEINE WITH EPITHELIAL ANTICANCER ACTIVITY: THEORETICAL STUDY OF GEOMETRIC, THERMOCHEMICAL AND SPECTROMETRIC DATA

Models validation in QSAR, pharmacophore, docking, and others, can ensure the accuracy and reliability of future predictions in design and selection of molecules with biological activity. In these study, the caffeine molecule was optimized using Hartree-Fock (HF) and Density Functional Theory (DFT/B3LYP) methods, with seven basis sets. Linear correlation data, errors and RMSD values between theoretical and experimental data allowed us to classify the methods and basis sets for evaluating their correspondence with experimental data (geometric parameters, heat capacity, as well as Infrared, Raman and NMR spectra). The HF method has shown the highest correspondence with the experimental data, occupying the top-five rank of the general classification. The HF/6-31G** method was the best one classified and it can be used to model the biological activity of the caffeine molecule

VALIDATION OF COMPUTATIONAL METHODS APPLIED IN MOLECULAR MODELING OF CAFFEINE WITH EPITHELIAL ANTICANCER ACTIVITY: THEORETICAL STUDY OF GEOMETRIC, THERMOCHEMICAL AND SPECTROMETRIC DATA

<div><p>Models validation in QSAR, pharmacophore, docking, and others, can ensure the accuracy and reliability of future predictions in design and selection of molecules with biological activity. In these study, the caffeine molecule was optimized using Hartree-Fock (HF) and Density Functional Theory (DFT/B3LYP) methods, with seven basis sets. Linear correlation data, errors and RMSD values between theoretical and experimental data allowed us to classify the methods and basis sets for evaluating their correspondence with experimental data (geometric parameters, heat capacity, as well as Infrared, Raman and NMR spectra). The HF method has shown the highest correspondence with the experimental data, occupying the top-five rank of the general classification. The HF/6-31G** method was the best one classified and it can be used to model the biological activity of the caffeine molecule.</p></div