The characterisation of the protective film formed by benzotriazole on the 90/10 copper-nickel alloy surface in H2SO4 media

The nature of the protective film formed by benzotriazole (BTAH) on the surface of the 90/10 CuNi alloy in deaerated 0.5 mol L-1 H2SO4 solution containing Fe(III) ions as oxidant was investigated by weight-loss, calorimetric measurements, and by surface-enhanced Raman spectroscopy (SERS). The SERS measurements show that the protective film is composed by the [Cu(I)BTA](n), polymeric complex and that the BTAH molecules are also adsorbed on the electrode surface. A modification of the BET isotherm for adsorption of gases ill solids is proposed to describe the experimental results obtained from weight-loss experiments that suggest an adsorption in multilayers. Electrochemical studies of copper and nickel in 0.5 mol L-1 H2SO4 in presence and absence of BTAH have also been made as an aid to interpret the results. The calculated adsorption free energy of the cuprous benzotriazolate on the surface of the alloy is in accordance with the value for pure copper. (C) 2007 Elsevier Ltd. All rights reserved.

Study of electrochemical behavior of azoles for AISI 430 stainless steel in H(2)SO(4) 1 mol L(-1)

Corrosion is an undesirable process that occurs in metallic materials. Studied was the effect of inhibiting Benzotriazole (BTAH), Benzimidazole (BZM) and Indole in different concentrations-for the stainless steel (SS) AISI 430 in H(2)SO(4) mol The techniques employed this research were: anodic potenciostatic polarisation, electrochemical impedance spectroscopy, optical microscopy and scanning electron microscopy The curves of anodic polarisation showed that BTAH, BZM and Indol act as corrosion inhibitors for 430 SS, at concentrations of 1x10(-3) and 5x10(-4) mol L(-1) but do not inhibit corrosion for concentrations equal to or less than 1x10(-4) mol L(-1). The in-crease of the efficiency in relation to the inhibitory substances studied followed this order: Indol

Electrochemical behavior of the cistein and diphosfonate for stainless steel in media of HCl 1 mol L(-1)

Amino acids and self assembled monolayers (SAM`s) have been studied as to their inhibiting action on the corrosion of metallic materials. The objective of work is to study the electrochemical behavior of the cisteincisteine, the diphosfonate and the mixture of both in inhibiting the action of corrosion on stainless steel 304 in HCl 1 molL(-1). As the following techniques were used: open circuit potential (OCP), potenciostatic anodic polarization (A P), chronoamperomeny (CA), electrochemical impedance spectroscopy (EIS) and optical microscopy (OM). The results of CA showed that cisteine has a double effect, catalytic and inhibiting, in function of the immersion time of the metallic part in the electrolytic solution. AP curves have shown lesser current density for the system containing cisteine diphosfonate suggesting an inhibiting synergic action. These results have been confirmed by EIS and OM.

Caffeic and chlorogenic acids in Ilex paraguariensis extracts are the main inhibitors of AGE generation by methylglyoxal in model proteins

The present study concentrates on the evaluation of the anti-glycation effect of some bioactive substances present in yerba mate (Ilex paraguariensis): 5-caffeoylquinic acid, caffeic acid and a sapogenin (oleanolic acid). Bovine serum albumin and histones were incubated in the presence of methylglyoxal with or without the addition of 5-caffeoylquinic acid, caffeic acid and oleanolic acid. After the incubation period, advanced glycation end product (AGE) fluorescence spectra were performed and protein structural changes were evaluated by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis. Chlorogenic acid, caffeic acid are the main substances responsible for the anti-glycation effect of mate tea. (C) 2009 Elsevier B.V. All rights reserved.

Corrosion behavior of pure titanium in artificial saliva solution

The biocompatibility of commercially pure (cp) titanium stems from its chemical stability within an organism, due to a fine film of impermeable titanium oxide covering the metal surface, which guarantees its resistance to corrosion. Despite its biocompatible characteristic, this material does not promote the formation of a hydroxyapatite layer, therefore, many research groups have sought to alter the material`s surface, introducing modifications that might influence corrosion resistance. The electrochemical behavior of cp Ti, with hydroxyapatite coating and without hydroxyapatite coating, commonly used in implant materials, was investigated using an artificial saliva solution at 25 degrees C and pH=7.4. In the conditions of the study it was observed that the hydroxyapatite layer influences the properties of corrosion resistance. This study of the behavior of cp Ti with and without hydroxyapatite coating, in naturally aerated artificial saliva solution at 25 degrees C, was based on open circuit potential measurements and potentiodynamic polarization curves. At approximately 1x10(-6) A/cm(2) the potential for cp Ti with and without hydroxyapatite coating begins to increase at a faster rate, but at -74mV (SCE) for coated cp Ti and at 180mV (SCE) for uncoated cp Ti the increase in potential begins to slow. This behavior, characterized by a partial stabilization of current density, indicates that in those potential ranges a protective passive film is formed.

Effects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murine Trypanosoma cruzi infection

Prostaglandins are known to be produced by macrophages when challenged with Trypanosoma cruzi, the etiological agent of Chagas` disease. It is not known whether these lipid mediators play a role in oxidative stress in host defenses against this important protozoan parasite. In this study, we demonstrated that inducible cyclooxygenase-mediated prostaglandin production is a key chemical mediator in the control of parasite burden and erythrocyte oxidative stress during T. cruzi infection in C57BL/6 and BALB/c mice, prototype hosts for the study of resistance and susceptibility in murine Chagas` disease. The results suggested the existence of at least two mechanisms of oxidative stress, dependent or independent with regard to the nitric oxide and cyclooxygenase pathway, where one or the other is more evident depending on the mouse strain.

Diapocynin versus apocynin as pretranscriptional inhibitors of NADPH oxidase and cytokine production by peripheral blood mononuclear cells

Apocynin has been extensively used as an inhibitor of NADPH oxidase (NOX) in many experimental models using phagocytic and non-phagocytic cells. Currently, there is some controversy about the efficacy of apocynin in non-phagocytic cells, but in phagocytes the reported results are consistent, which could be due to the presence of myeloperoxidase in these cells. This enzyme has been proposed as responsible for activating apocynin by generating its dimer, diapocynin, which is supposed to be the active compound that prevents NADPH oxidase complex assembly and activation. Here, we synthesized diapocynin and studied its effect on inhibition of gp91(phox) RNA expression. We found that diapocynin strongly inhibited the expression of gp91(phox)mRNA in peripheral blood mononuclear cells (PBMC). Only at a higher concentration, apocynin was able to exert the same effect. We also compared the apocynin and diapocynin efficacy as inhibitors of tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) production in response to lipopolysaccharide (LPS)-activated PBMC. Although apocynin did inhibit TNF-alpha production, diapocynin had a much more pronounced effect, on both TNF-alpha and IL-10 production. In conclusion, these findings suggest that the bioconversion of apocynin to diapocynin is an important issue not limited to enzymatic activity inhibition, but also for other biological effects as gp91(phox) mRNA expression and cytokine production. Hence, as diapocynin can be easily prepared from apocynin, a one-step synthesis, we recommend its use in studies where the biological effects of apocynin are searched. (C) 2010 Elsevier Inc. All rights reserved.

Metallopeptidase inhibitors arrest vital biological processes in the fungal pathogen Scedosporium apiospermum

P>Scedosporium apiospermum is an emerging agent of opportunistic mycoses in humans. Previously, we showed that mycelia of S. apiospermum secreted metallopeptidases which were directly linked to the destruction of key host proteins. In this study, we analysed the effect of metallopeptidase inhibitors on S. apiospermum development. As germination of inhaled conidia is a crucial event in the infectious process of S. apiospermum, we studied the morphological transformation induced by the incubation of conidia in Sabouraud-dextrose medium at 37 degrees C. After 6 h, some conidia presented a small projection resembling a germ-tube. A significant increase, around sixfold, in the germ-tube length was found after 12 h, and hyphae were exclusively observed after 24 h. Three distinct metallopeptidase inhibitors were able to arrest the transformation of conidia into hyphae in different ways; for instance, 1,10-phenanthroline (PHEN) completely blocked this process at 10 mu mol l-1, while ethylenediamine tetraacetic acid (EDTA) and ethylene glycol-bis (beta-aminoethyl ether; EGTA) only partially inhibited the differentiation at up to 10 mmol l-1. EGTA did not promote any significant reduction in the conidial growth, while PHEN and EDTA, both at 10 mmol l-1, inhibited the proliferation around 100% and 65%, respectively. The secretion of polypeptides into the extracellular environment and the metallopeptidase activity secreted by mycelia were completely inhibited by PHEN. These findings suggest that metallo-type enzymes could be potential targets for future therapeutic interventions against S. apiospermum.

In situ impedance spectroscopy study of the electrochemical corrosion of Ti and Ti-6Al-4V in simulated body fluid at 25 degrees C and 37 degrees C

The corrosion resistance of Ti and Ti-6Al-4V was investigated through electrochemical impedance spectroscopy, EIS, potentiodynamic polarisation curves and UV-Vis spectrophotometry. The tests were done in Hank solution at 25 degrees C and 37 degrees C. The EIS measurements were done at the open circuit potential at specific immersion times. An increase of the resistance as a function of the immersion time was observed, for Ti (at 25 degrees C and 37 degrees C), and for Ti-6Al-4V (at 25 degrees C), which was interpreted as the formation and growth of a passive film on the metallic surfaces. (C) 2009 Elsevier Ltd. All rights reserved.

Investigation of AISI 1040 steel corrosion H(2)S solution containing chloride ions by digital image processing coupled with in electrochemical techniques

This paper presents a study of AISI 1040 steel corrosion in aqueous electrolyte of acetic acid buffer containing 3.1 and 31 x 10(-3) mol dm(-3) of Na(2)S in both the presence and absence of 3.5 wt.% NaCl. This investigation of steel corrosion was carried out using potential polarization, and open-circuit and in situ optical microscopy. The morphological analysis and classification of types of surface corrosion damage by digital image processing reveals grain boundary corrosion and shows a non-uniform sulfide film growth, which occurs preferentially over pearlitic grains through successive formation and dissolution of the film. (C) 2011 Elsevier Ltd. All rights reserved.

Quantitative structure-activity relationships for a series of inhibitors of cruzain from Trypanosoma cruzi: Molecular modeling, CoMFA and CoMSIA studies

Human parasitic diseases are the foremost threat to human health and welfare around the world. Trypanosomiasis is a very serious infectious disease against which the currently available drugs are limited and not effective. Therefore, there is an urgent need for new chemotherapeutic agents. One attractive drug target is the major cysteine protease from Trypanosoma cruzi, cruzain. In the present work, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies were conducted on a series of thiosemicarbazone and semicarbazone derivatives as inhibitors of cruzain. Molecular modeling studies were performed in order to identify the preferred binding mode of the inhibitors into the enzyme active site, and to generate structural alignments for the three-dimensional quantitative structure-activity relationship (3D QSAR) investigations. Statistically significant models were obtained (CoMFA. r(2) = 0.96 and q(2) = 0.78; CoMSIA, r(2) = 0.91 and q(2) = 0.73), indicating their predictive ability for untested compounds. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the information gathered from the 3D CoMFA and CoMSIA contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of cruzain inhibitors, and should be useful for the design of new structurally related analogs with improved potency. (C) 2009 Elsevier Inc. All rights reserved.

Discovery of novel Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase inhibitors

Based on its essential role in the life cycle of Trypanosoma cruzi, the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) has been considered a promising target for the development of novel chemotherapeutic agents for the treatment of Chagas` disease. In the course of our research program to discover novel inhibitors of this trypanosomatid enzyme, we have explored a combination of structure and ligand-based virtual screening techniques as a complementary approach to a biochemical screening of natural products using a standard biochemical assay. Seven natural products, including anacardic acids,. avonoid derivatives, and one glucosylxanthone were identified as novel inhibitors of T. cruzi GAPDH. Promiscuous inhibition induced by nonspecific aggregation has been discarded as specific inhibition was not reversed or affected in all cases in the presence of Triton X-100, demonstrating the ability of the assay to find authentic inhibitors of the enzyme. The structural diversity of this series of promising natural products is of special interest in drug design, and should therefore be useful in future medicinal chemistry efforts aimed at the development of new GAPDH inhibitors having increased potency. (C) 2009 Elsevier Ltd. All rights reserved.

Effectiveness of commercial inhibitors against subtype F HIV-1 protease

Subtype F wild type HIV protease has been kinetically characterized using six commercial inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) commonly used for HIV/AIDS treatment, as well as inhibitor TL-3 and acetylpepstatin. We also obtained kinetic parameters for two multi-resistant proteases (one of subtype B and one of subtype F) harboring primary and secondary mutations selected by intensive treatment with ritonavir/nelfinavir. This newly obtained biochemical data shows that all six studied commercially available protease inhibitors are significantly less effective against subtype F HIV proteases than against HIV proteases of subtype B, as judged by increased K(i) and biochemical fitness (vitality) values. Comparison with previously reported kinetic values for subtype A and C HIV proteases show that subtype F wild type proteases are significantly less susceptible to inhibition. These results demonstrate that the accumulation of natural polymorphisms in subtype F proteases yields catalytically more active enzymes with a large degree of cross-resistance, which thus results in strong virus viability.

Anacardic acid derivatives as inhibitors of glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi

Chagas` disease, a parasitic infection caused by the flagellate protozoan Trypanosoma cruzi, is a major public health problem affecting millions of individuals in Latin America. On the basis of the essential role in the life cycle of T. cruzi, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been considered an attractive target for the development of novel antitrypanosomatid agents. In the present work, we describe the inhibitory effects of a small library of natural and synthetic anacardic acid derivatives against the target enzyme. The most potent inhibitors, 6-n-pentadecyl-(1) and 6-n-dodecylsalicilic acids (10e), have IC(50) values of 28 and 55 mu M, respectively. The inhibition was not reversed or prevented by the addition of Triton X-100, indicating that aggregate-based inhibition did not occur. In addition, detailed mechanistic characterization of the effects of these compounds on the T. cruzi GAPDH-catalyzed reaction showed clear noncompetitive inhibition with respect to both substrate and cofactor. (C) 2008 Elsevier Ltd. All rights reserved.

In silico screening of HIV-1 non-nucleoside reverse transcriptase and protease inhibitors

Two targets, reverse transcriptase (RT) and protease from HIV-1, were used during the past two decades to the discovery of non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) that belong to the arsenal of the antiretroviral therapy. Herein these enzymes were chosen as templates for conducting a computer-aided ligand design. Ligand and structure-based drug designs were the starting points to select compounds from a database bearing more than five million compounds by means of cheminformatic tools. New promising lead structures are retrieved from the database, which are open to acquisition and test. Classes of molecules already described as NNRTI or PI in the literature also came out and were useful to prove the reliability of the workflow, and thus validating the work carried out so far. (c) 2007 Elsevier Masson SAS. All rights reserved.