Inibidores da HIV-integrase: Potencial abordagem farmacológica para tratamento da AIDS

AIDS has the HIV as its etiological agent. Researches has been done to find new pharmacological agents to be used in therapy, because of problems of resistance and side effects. The HIV-integrase inhibitors are some of those new agents that are being studied. This updating focusses on the fundamental information about HIV and HIV-integrase and the main methods being used to develop these new drugs, with examples for each case.

Simultaneous determination of Cd and Pb in antibiotics used in sugar-cane fermentation process by GFAAS

A method has been developed for the simultaneous determination of Cd and Pb in antibiotics used in sugar-cane fermentation by GFAAS. The integrated platform of transversely heated graphite atomizer was treated with tungsten to form a coating of tungsten carbide. Six samples of commercial solid antibiotics were analyzed by injecting 20 μL of digested samples into the pretreated graphite platform with co-injection of 5 μL of 1000 mg L-1 Pd as chemical modifier. Samples were mineralized in a closed-vessel microwave-assisted acid-digestion system using nitric acid plus hydrogen peroxide. The pyrolysis and atomization temperatures of the heating program of the atomizer were selected as 600°C and 2200°C, respectively. The calculated characteristic mass for Cd and Pb was 1.6 pg and 42 pg, respectively. Limits of detection (LOD) based on integrated absorbance were 0.02 μg L -1 Cd and 0.7 μg L-1 Pb and the relative standard deviations (n = 10) for Cd and Pb were 5.7% and 8.0%, respectively. The recoveries of Cd and Pb added to the digested samples varied from 91% to 125% (Cd) and 80% to 112% (Pb).

Aspectos químicos, biológicos e etnofarmacológicos do gênero Cassia

Species of Cassia are widely distributed in tropical and subtropical regions throughout the world, and have been extensively investigated chemically and pharmacologically.They are known to be a rich source of phenolic derivatives, most of them with important biological and pharmacological properties. Some Asian, African and Indian tribes use these species as a laxative, purgative, antimicrobial, antipyretic, antiviral and anti-inflammatory agent. Among a number of other classes of secondary metabolites, such as anthracene derivatives, antraquinones, steroids and stilbenoids, biologically active piperidine alkaloids are an especially important bioactive class of compounds that showed to be restricted to a small group of Cassia species. In this paper we present an overview of the chemical, biological and ethnopharmacological data on Cassia piblished in the literature.

Pró-fármaco ativado por enzima, uma estratégia promissora na quimioterapia

Strategies that promote selective activation of prodrugs by enzymes can be divided into two major classes: 1) deliver of a monoclonal antibody-enzyme immunoconjugate that can recognize a specific antigen and promote the prodrug to a citotoxic drug, with a high selectivity for the target cells, and 2) selective gene delivery encoding an enzyme that can promote the prodrug to a citotoxic drug for the target cells. In this article are discussed ADEPT (antibody-directed enzyme prodrug therapy), GDEPT (gene-directed enzyme prodrug therapy), VDEPT (virus-directed enzyme prodrug therapy), GPAT (genetic prodrug activation therapy) and PDEPT (polymer-directed enzyme prodrug therapy) approaches, their clinical trials, advantages, disadvantages and perspectives.

Isolation of lignans glycosides from Alibertia sessilis (Vell.) K. Schum. (Rubiaceae) by preparative high-performance liquid chromatography

Enantiomeric aglycone lignans contained in a mixture were separated from a fraction of the extract of the stems of Alibertia sessilis (Vell.) K. Schum. (Rubiaceae) by preparative high-performance liquid chromatography. An efficient and fast separation can be achieved with methanol-water (30:70, v/v). Their structures were identified as (+)-lyoniresinol 3α-O-β-glucopyranoside and (-)-lyoniresinol 3α-O-β-glucopyranoside, being reported for the first time in Rubiaceae.

Does cotinine act upon reactive oxygen species and peroxidases?

Nicotine, an oxidizing agent, is certainly one of the most widely used alkaloids in the world. It is, together with its main metabolite, cotinine, responsible for tobacco-dependence. The use of tobacco is closely associated with lung disease, morphological leukocyte modification and generation of oxidant species. The aim of this study was to look for a possible relationship between cotinine, oxidant species generation and oxidative processes. After studying the action of cotinine in some chemical oxidation models and on the enzymatic kinetics of peroxidases (myeloperoxidase and horseradish peroxidase), we concluded that cotinine does not act directly upon H 2O 2, HOCl, taurine chloramines, horseradish peroxidase or myeloperoxidase.

Estudo da influência dos íons K+, Mg2+, SO4 2- e CO3 2- na cristalização biomimética de fosfato de cálcio amorfo (ACP) e conversão a fosfato octacálcico (OCP)

The crystallization of hydroxyapatite (HA) in aqueous solution can be described by the mechanism ACP → OCP → HA. In this work, it was studied the influence of K+, Mg2+, SO4 2- AND CO3 2- ions in the formation of ACP and in its conversion to OCP, using biomimetic coatings on metallic substrates of commercially pure titanium (Ti c.p.). The results showed that Mg2+ and CO3 2- ions favored both the formation of ACP and its conversion to OCP. Differently, K+ and SO4 2- ions did not influence the formation of ACP and, consequently, interfered in the conversion to OCP.

Estudo da dissolução oxidativa microbiológica de uma complexa amostra mineral contendo pirita (FeS2), pirrotita (Fe 1-XS) e molibdenita (MoS2)

This work aims to study the oxidation of a complex molybdenite mineral which contains pyrite and pyrrotite, by Acidithiobacillus ferrooxidans. This study was performed by respirometric essays and bioleaching in shake flasks. Respirometric essays yielded the kinetics of mineral oxidation. The findings showed that sulfide oxidation followed classical Michaelis-Menten kinetics. Bioleaching in shake flasks allowed evaluation of chemical and mineralogical changes resulting from sulfide oxidation. The results demonstrated that pyrrotite and pyrite were completely oxidized in A. ferrooxidans cultures whereas molybdenite was not consumed. These data indicated that molybdenite was the most recalcitrant sulfide in the sample.

Clerodane diterpenes from leaves of Casearia sylvestris swartz

Ethanolic extracts of the leaves of Casearia sylvestris yielded a novel clerodane diterpene, 15-hydroxy-3-cleroden-2-one, together with the known diterpenes (-)-hardwickiic acid, reported for the first time from this species, and casearins B and G, previously isolated from C. sylvestris. The structures of all four compounds were determined by spectrometric analysis. The new clerodane diterpene and (-)-hardwickiic acid contain structural features that are completely different from the highly oxygenated casearins and casearvestrins isolated from C. sylvestris.

Determinação de fármacos diuréticos em associação por cromatografia em camada delgada e espectrofotometria

A rapid, sensitive and reliable thin-layer chromatography/spectrophotometry screening procedure was developed for quantitative determination of diuretics associated in pharmaceutical dosage forms. The chromatographic method employed microcrystalline cellulose and butanol : acetic acid : water (4:1:1) or amilic alcohol : ammonium hydroxide 25% (9:1) as mobile phases and detection by U.V. light. The drugs were extracted using a simple procedure and were quantified by U.V. spectrophotometry. Results varied from 97.5 to 102.5% and are similar to those obtained by conventional methods. This method of quantification of diuretics is promising for quality control of drugs.

Determination of atenolol in pharmaceutical formulations by diffuse reflectance spectroscopy

A simple analytical method for quantification of atenolol in pharmaceutical formulations by diffuse reflectance spectroscopy is described. The method is based on the reaction, on the filter paper surface, between the drug and p-chloranil producing a colored compound. The best reaction conditions were obtained with 20 μL of atenolol solution and 20 μL of p-chloranil. All reflectance measurements were carried out at 550 nm and the linear range was from 1.13×10-2 to 7.88×10-2 mol L-1 (r = 0.9992). The limit of detection was 2.80 × 10-3 mol L-1. The proposed method was successfully applied to analysis of different commercial brands of pharmaceutical formulations and the results obtained by the proposed method were in good agreement with those obtained using the British Pharmacopoeia method.

A simple spectrophotometric method for the determination of methyldopa using p-chloranil in the presence of Hydrogen Peroxide

A simple, rapid and sensitive spectrophotometric method has been developed for the determination of methyldopa in pharmaceutical formulations. The method is based on the reaction between tetrachloro-p-benzoquinone (p-chloranil) and methyldopa, accelerated by hydrogen peroxide (H 2O 2), producing a violet-red compound (λmax = 535 nm) at ambient temperature (25.0 ± 0.2°C). Experimental design methodologies were used to optimize the measurement conditions. Beer's law is obeyed in a concentration range from 2.10 × 10 -4 to 2.48 × 10 -3 mol L -1 (r = 0.9997). The limit of detection was 7.55 × 10 -6 mol L -1 and the limit of quantification was 2.52 × 10 -5 mol L -1. The intraday precision and interday precision were studied for 10 replicate analyses of 1.59 × 10 -3 mol L -1 methyldopa solution and the respective coefficients of variation were 0.7 and 1.1%. The proposed method was successfully applied to the determination of methyldopa in commercial brands of pharmaceuticals. No interferences were observed from the common excipients in the formulations. The results obtained by the proposed method were favorably compared with those given by the Brazilian Pharmacopoeia procedure at 95% confidence level.

Espectrofotometria de longo caminho óptico em espectrofotô metro de duplo-feixe convencional: uma alternativa simples para investigações de amostras com densidade óptica muito baixa

We describe the design and tests of a set-up mounted in a conventional double beam spectrophotometer, which allows the determination of optical density of samples confined in a long liquid core waveguide (LCW) capillary. Very long optical path length can be achieved with capillary cell, allowing measurements of samples with very low optical densities. The device uses a custom optical concentrator optically coupled to LCW (TEFLON® AF). Optical density measurements, carried out using a LCW of ̃ 45 cm, were in accordance with the Beer-Lambert Law. Thus, it was possible to analyze quantitatively samples at concentrations 45 fold lower than that regularly used in Spectrophotometric measurements.

Thermal behaviour of succinic acid, sodium succinate and its compounds with some bivalent transitions metal ions in dynamic N 2 and CO 2 atmospheres

Thermal stability and thermal decomposition of succinic acid, sodium succinate and its compounds with Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) were investigated employing simultaneous thermogravimetry and differential thermal analysis (TG-DTA) in nitrogen and carbon dioxide atmospheres and TG-FTIR in nitrogen atmosphere. On heating, in both atmospheres the succinic acid melt and evaporate, while for the sodium succinate the thermal decomposition occurs with the formation of sodium carbonate. For the transition metal succinates the final residue up to 1180 °C in N 2 atmosphere was a mixture of metal and metal oxide in no simple stoichiometric relation, except for Zn compound, where the residue was a small quantity of carbonaceous residue. For the CO 2 atmosphere the final residue up to 980 °C was: MnO, Fe 3O 4, CoO, ZnO and mixtures of Ni, NiO and Cu, Cu 2O.

Determination of copper at wide range concentrations using instrumental features of high-resolution continuum source flame atomic absorption spectrometry

This work describes a method to determine Cu at wide range concentrations in a single run without need of further dilutions employing high-resolution continuum source flame atomic absorption spectrometry. Different atomic lines for Cu at 324. 754 nm, 327. 396 nm, 222. 570 nm, 249. 215 nm and 224. 426 nm were evaluated and main figures of merit established. Absorbance measurements at 324. 754 nm, 249. 215 nm and 224. 426 nm allows the determination of Cu in the 0. 07-5. 0 mg L -1, 5. 0-100 mg L -1 and 100-800 mg L -1 concentration intervals respectively with linear correlation coefficients better than 0. 998. Limits of detection were 21 μg L -1, 310 μg L -1 and 1400 μg L -1 for 324. 754 nm, 249. 215 nm and 224. 426 nm, respectively and relative standard deviations (n = 12) were ≤ 2. 7%. The proposed method was applied to water samples spiked with Cu and the results were in agreement at a 95% of confidence level (paired t-test) with those obtained by line-source flame atomic absorption spectrometry.