Physico-chemical characterization of inclusion complex between hydroxymethylnitrofurazone and hydroxypropyl-beta-cyclodextrin

Hydroxymethylnitrofurazone (NFOH) is a prodrug that is active against Trypanosoma cruzi. It however presents low solubility and high toxicity. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) can be used as a drug-delivery system for NFOH modifying its physico-chemical properties. The aim of this work is to characterize the inclusion complex between NFOH and HP-beta-CD. The rate of NFOH release decreases after complexation and thermodynamic parameters from the solubility isotherm studies revealed that a stable complex is formed (deltaGº= 1.7 kJ/mol). This study focuses on the physico-chemical characterization of a drug-delivery formulation that comes out as a potentially new therapeutic option for Chagas disease treatment.FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Theoretical and voltammetric studies of 5-Nitro-heterocyclic derivatives with potential trypanocidal activities

Stereoelectronic properties of nitro-heterocyclic bioisosteric congeners were investigated using theory-level quantum chemistry and cyclic voltammetry with the goal of determining physico-chemical properties that affect the redox potential of the nitro group. Molecular geometry, physicochemical properties and stereoelectronic surfaces, such as molecular electrostatic potential, and HOMO and LUMO orbitalar distributions, were calculated using the AM1 semiempirical method. The redox potential of nitro-heterocyclic compounds, which corresponds to the (Ar-NO2/Ar-NO2•- ) redox couple, was measured in aprotic media (DMSO and 0.1 mol L-1 Bu4NH4BF4) using glassy carbon as working electrode, Pt wire, Ag/AgCl, KCl(sat) as counter and reference electrodes, respectively. Analysis of minimal energy conformers of all derivatives indicated a break in structural planarity located between the hydrazine nitrogen and benzamide moiety. No statistical correlation was obtained using the PLS regression method, taking in account all physicochemical properties and the redox potential, which might result from the lack of coplanarity effect in the molecular structure of the compounds

Physico-chemical characterization of inclusion complex between hydroxymethylnitrofurazone and hydroxypropyl-b-cyclodextrin

Hydroxymethylnitrofurazone (NFOH) is a prodrug that is active against Trypanosoma cruzi. It however presents low solubility and high toxicity. Hydroxypropyl-b-cyclodextrin (HP-b-CD) can be used as a drug-delivery system for NFOH modifying its physico-chemical properties. The aim of this work is to characterize the inclusion complex between NFOH and HP-b-CD. The rate of NFOH release decreases after complexation and thermodynamic parameters from the solubility isotherm studies revealed that a stable complex is formed (DGº= 1.7 kJ/mol). This study focuses on the physico-chemical characterization of a drug-delivery formulation that comes out as a potentially new therapeutic option for Chagas disease treatment312290295COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP00019-08-0305/03045-9; 04/02091-4; 06/00787-

Desenvolvimento de um modelo para avaliar o nível de manutenção Lean de uma organização : caso de estudo

Trabalho final de mestrado para obtenção do grau de mestre em Engenharia MecânicaA criação de um modelo de avaliação Lean é importante para criar boas práticas a aplicar na área da manutenção, como principio de uma atividade que utiliza ferramentas Lean e consciente de todas as suas vantagens. A implementação de filosofia Lean na manutenção visa melhorar o planeamento e a programação das atividades, aumentar a produtividade, motivar os trabalhadores, ajudar na introdução de novos hábitos e de novas atitudes no trabalho e ainda identificar os desperdícios que devem ser eliminados. A competitividade e o preço excessivo dos produtos (bens ou serviços) que o cliente final não quer pagar, faz com que as empresas públicas e privadas tomem medidas para evitar todo o tipo de desperdícios, rentabilizando ao máximo a sua cadeia de valor. A filosofia Lean foi uma das formas encontradas para identificar e eliminar alguns desses desperdícios, melhorando o processo produtivo e, desta forma, tornando as organizações mais competitivas. O Lean tem várias ferramentas podendo ser aplicadas em diversas áreas. Uma dessas áreas é a manutenção, onde se pretende que os equipamentos operem sem interrupções e com uma produção de qualidade. Algumas das ferramentas do Lean encaixam-se perfeitamente na área da manutenção para identificação de desperdícios, criação de valor, realização de planeamento, melhoria do sistema de trabalho na organização e até no próprio desenvolvimento dos trabalhadores. A presente dissertação visa mostrar algumas das ferramentas mais comuns da filosofia Lean com aplicabilidade na manutenção de equipamentos de apoio à atividade de um serviço publico e ao desenvolvimento de um modelo de avaliação com apresentação através de estudo de caso. No trabalho infra são apresentadas diversas ferramentas Lean, nomeadamente 5s, trabalho padronizado, (standardwork uniformização), gestão visual (andon), melhoria continua (kaisen), mapeamento fluxo de valor na manutenção (MVSM), SIPOC, gestão visual, 5w, ciclo PDCA. O modelo de avaliação está estruturado em 3 grandes áreas “Clientes”, “Organização” e “Fornecedores”, vai subdividir-se em 7 critérios e 60 atributos. Dos 60 atributos, foram desenvolvidos 6 e que compõem mais de 70 atributos, perfazendo mais de 130 no final o modelo proposto neste trabalho.The creation of a lean evaluation model is important to create good practice in the field of maintenance as the principle of an activity that uses lean tools aware of all its advantages. Implementing Lean's philosophy of maintenance aims to improve planning and scheduling of activities, increase productivity, motivate employees, assist in introducing new habits and new attitudes at work, and identify the wastes that need to be eliminated. Competitiveness and the excessive price of products (goods or services) that the final customer does not want to pay, makes public and private companies take measures to avoid all types of waste, making the most of its value chain. The Lean philosophy was one of the ways found to identify and eliminate some of these wastes, improving the production process and thus making companies more competitive. Lean has several tools that can be applied in several areas. One of these areas is maintenance, where the equipment is intended to operate without interruption and with a quality production. Some of Lean's tools fit perfectly into the maintenance area for waste identification, value creation. The present dissertation aims to show some of the most common tools of the Lean philosophy with applicability in the maintenance of equipment to support the activity of a public service and the development of an evaluation model with presentation through case study. In the work below are presented several Lean tools, namely 5s, standardized work, (standardwork standardization), visual management (andon), continuous improvement (kaisen), maintenance value flow mapping (MVSM), SIPOC, visual management, 5w, cycle PDCA. The avaliation model is structured in 3 large areas "Customers", "Organization" and "Suppliers", will be subdivided into 7 criteria and 60 attributes. Of the 60 attributes were developed 6 and that make up more than 70 attribute attributes, preferring more than 130 at the end the model proposeN/

Hologram QSAR Studies of Antiprotozoal Activities of Sesquiterpene Lactones

Infectious diseases such as trypanosomiasis and leishmaniasis are considered neglected tropical diseases due the lack for many years of research and development into new drug treatments besides the high incidence of mortality and the lack of current safe and effective drug therapies. Natural products such as sesquiterpene lactones have shown activity against T. brucei and L. donovani, the parasites responsible for these neglected diseases. To evaluate structure activity relationships, HQSAR models were constructed to relate a series of 40 sesquiterpene lactones (STLs) with activity against T. brucei, T. cruzi, L. donovani and P. falciparum and also with their cytotoxicity. All constructed models showed good internal (leave-one-out q2 values ranging from 0.637 to 0.775) and external validation coefficients (r2test values ranging from 0.653 to 0.944). From HQSAR contribution maps, several differences between the most and least potent compounds were found. The fragment contribution of PLS-generated models confirmed the results of previous QSAR studies that the presence of α,β-unsatured carbonyl groups is fundamental to biological activity. QSAR models for the activity of these compounds against T. cruzi, L. donovani and P. falciparum are reported here for the first time. The constructed HQSAR models are suitable to predict the activity of untested STLs

Síntese de heterociclos bioativos derivados do ferroceno

The discovery of ferrocene marked one of the points of departure for modern organometallic chemistry. In general, the compounds of ferrocene derivatives are widely applied in several areas. One of the most important applications of ferrocene is the development of more active drugs, especially in cases where there is resistance to current drugs. Bioactive agents containing ferrocene have proven effective in combating diseases such as cancer, malaria, HIV, Alzheimer and conditions caused by fungi and bacteria. In this context, the present paper aims to highlights the synthesis of heterocycles containing ferrocene moiety and their use in medicinal chemistry

Enantioselective Arylations Catalyzed by Carbohydrate-Based Chiral Amino Alcohols

The application of carbohydrate-derived amino alcohols in the asymmetric arylation of aldehydes by using arylboronic acids as the source of transferable aryl groups is described. The best ligand is derived from the readily available sugar D-xylose and it mediates the addition of a range of arylboronic acids to various aromatic aldehydes in excellent yields and high enantiomeric excesses.Fundacao de Amparo Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Comissao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Identification, In Vitro Testing and Molecular Docking Studies of Microginins’ Mechanism of Angiotensin-Converting Enzyme Inhibition

Cyanobacteria are able to produce a wide range of secondary metabolites, including toxins and protease inhibitors, with diverse biological activities. Microginins are small linear peptides biosynthesized by cyanobacteria species that act against proteases. The aim of this study was to isolate and identify microginins produced by the LTPNA08 strain of Microcystis aeruginosa, as well as to verify their potential to inhibit angiotensin-converting enzyme (ACE; EC. 3.4.15.1) using in vitro and in silico methods. The fractionation of cyanobacterial extracts was performed by liquid chromatography and the presence of microginins was monitored by both LC-MS and an ACE inhibition assay. Enzyme inhibition was assayed by ACE with hippuryl-histidyl-leucine as the substrate; monitoring of hippuric acid was performed by HPLC-DAD. Isolated microginins were confirmed by mass spectrometry and were used to carry out the enzymatic assay. Molecular docking was used to evaluate microginin 770 (MG 770) and captopril (positive control), in order to predict similar binding interactions and determine the inhibitory action of ACE. The enzyme assay confirmed that MG 770 can efficiently inhibit ACE, with an IC50 equivalent to other microginins. MG 770 presented with comparable interactions with ACE, having features in common with commercial inhibitors such as captopril and enalaprilate, which are frequently used in the treatment of hypertension in humans

Electrochemical and Theoretical Studies on the Artesunate Reduction

Malaria is the most devastating tropical disease in the world and this scenario is worsened by the absence of effective treatment. However, the plasmodium resistance to artemisinin does not show clinical relevance. The drug mechanism of action is associated to the endoperoxide moiety breakage. Artesunate is a semi-synthetic derivative of artemisinin and its absorption is facilitated due to its higher solubility in water. As a sesquiterpene lactone, artesunate can be electrochemically reduced in aqueous media on the glassy carbon electrode, having been studied by cyclic voltammetry, square wave voltammetry and chronoamperometry. The artesunate voltammetric reduction is diffusion-controlled and significantly irreversible. Its reduction is pH-independent, but from pH = 6.0 the cathodic current values increase in alkaline media, indicating that the proton-equilibrium occurs after the electron transfer step. The an values calculated vary from 0.30 to 0.37, leading to the 0.0975 s-1 value for ks. From the chronoamperometric data, two electrons (1.9 ± 0.4) are involved in the reduction process, being confirmed by the exact number of electrons obtained for artemisinin (1.9 ± 0.2). According to these results and computational findings, both drugs have the same reduction mechanism with the breakage of the endoperoxide bridge and consequent diol-derivative formation followed by the deoxy analog stabilization through the existence of a set of reactions involving protonation and charge transfer steps on the electrode surface. DOI: http://dx.doi.org/10.17807/orbital.v12i3.1439</p