Resumo em Inglês:

The Canadian oil sands reserves are an important national resource with a large impact on the Canadian economy. Unfortunately, oil sands extraction processes generate toxic by-products called mature fine tailings that need to be stored in disposal ponds for a very long time before the land can be reclaimed. This serious environmental liability needs to be addressed to reduce the environmental footprint of oil sands operations in Canada. In our research group, we have been applying polymer reaction engineering principles to develop new polymer flocculants specifically designed to treat oil sands tailing ponds. This article gives an overview of the research activities in our laboratory in the area of water-soluble polymer flocculants for the efficient dewatering, consolidation and densification of mature fine tailings.

Resumo em Inglês:

It was developed a concise synthetic route resulting in the first syntheses of bis-Strychnos alkaloids (-)-sungucine, (-)-isosungucine, and (-)-strychnogucine B from commercially available (-)-strychnine. Employing a highly convergent synthetic strategy, it was demonstrated that both Strychnos monomers could be efficiently prepared from commercially available (-)-strychnine. The venerable Mannich reaction was enlisted to join the two Strychnos monomers in a biomimetic fashion. Subsequent epimerization and olefin isomerization yielded (-)-strychnogucine B. Functional group manipulation transformed (-)-strychnogucine B into (-)-sungucine and (-)-isosungucine. Computational chemistry was employed to rationalize the regiochemical course of key steps en route to the bis-Strychnos targets.

Resumo em Inglês:

Cancer is a complex disease which involves abnormalities of multiple cellular pathways. Current chemotherapeutic drugs are mainly designed to target the DNA and cell division. Therefore, in the present study, we have synthesized a new series of 1,2,3-triazolo-naphthalimide/phthalimide conjugates and evaluated their in vitro cytotoxicity against selected human cancer cells. Among the tested compounds, one of them displayed notable cytotoxic activity against A549 lung cancer cells with an IC50 (half maximal inhibitory concentration) value of 7.6 ± 0.78 µM. To determine the effect of this compound on cell viability, acridine orange/ethidium bromide (AO/EB) and 4',6-diamidino-2-phenylindole (DAPI) staining studies were performed. These apoptotic features were clearly indicating that the compound inhibited cell proliferation by apoptosis. Further, relative viscosity measurements and molecular docking studies with the most three active compounds indicated that these new compounds bind to DNA by intercalation.

Resumo em Inglês:

Drinking water samples taken from cafeteria sinks and water fountains in each of the 76 schools in the Winston-Salem/Forsyth County Schools (WSFCS) district (North Carolina, United States) were analyzed by inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) to determine As, Cd, Cr, Cu, Pb, Sb, Se and Tl. All samples from currently active schools tested below the maximum contaminant level (MCL) set for each element. Model-based clustering was employed to identify schools more prone to drinking water contamination. This multivariate approach may be used in a prevention program that can be tailored to specific school districts, with each school tested at a frequency compatible with its contamination risk level. Water flow stagnation during the summer break results in higher elemental concentrations in school drinking water, but a simple 5-60 min flushing procedure significantly reduces the contamination levels.

Resumo em Inglês:

The dichloromethane extract of the root bark of the Panamanian plant Cordia anisophylla J.S. Mill. (Boraginaceae) presented antifungal activity against a susceptible strain of Candida albicans in a bioautography primary screening. The susceptible strain was used to detect minor active compounds that would not have been detected using a classical approach. In order to identify the antimicrobial compounds, the active extract was fractionated by semi-preparative high-performance liquid chromatography and the fractions were submitted to the antifungal bioassay. This procedure enabled a precise localization of the antifungal compounds directly in the chromatogram of the crude extract and allowed for an efficient, targeted isolation. Four compounds were isolated, one of which is a new natural product. The structures were elucidated using spectroscopic methods. Their antifungal properties were evaluated by determination of the minimum inhibitory quantity and concentration by bioautography and dilution assay against a wild type strain of C. albicans.

Resumo em Inglês:

In lignin-first biorefining via reductive processes, lignocellulosic materials are deconstructed by the solvent extraction of lignin in the presence of a hydrogenation catalyst. This approach provides a route to the successful extraction and reductive passivation of lignin fragments to produce low molar mass lignin oils together with high-quality pulps. Herein, we present an investigation into the impact of process severity (i.e., cooking temperature) on the reductive processes taking place on the lignin fragments and uniformity of the product mixture. In addition to improving overall delignification yields (up to 87%) and producing low molar mass fragments, higher process temperatures led to the preferential cleavage of hydroxyl groups in monolignol sidechains via hydrodeoxygenation, yielding oils with lower oxygen content. By comparing products from both lignin-first biorefining and organosolv processes at various temperatures, we elucidate key performance differences and outline routes to increased chemical uniformity in lignin streams. Overall, this study outlines clearly the importance of process temperature in the deconstruction of lignocellulose by lignin-first biorefining when producing highly depolymerized lignin products. This study points out a trade-off in the effect of temperature upon delignification and increase in product mixture complexity, which needs to be carefully optimized for the scale-up of lignin-first technologies.

Resumo em Inglês:

Anthocyanins are the natural plant pigments responsible for most of the red, blue and purple colors of flowers and fruit. One method of stabilization of the color of anthocyanins in nature is intramolecular copigmentation, in which a copigment molecule covalently attached to one of the sugar residues complexes with the anthocyanin cation chromophore. In the present work, two quantum chemical methodologies, time-dependent density functional theory (TD-DFT) and second.order algebraic diagrammatic construction (ADC(2)), were employed to predict the absorption spectra in vacuum and conductor-like screening model (COSMO) water of a natural anthocyanin containing an ester of coumaric acid (copigment) bound to the sugar residue of a cyanidin chromophore. ADC(2) in water adequately reproduces the experimental spectra with and without intramolecular copigmentation, pointing to this theoretical technique as a promising approach for predicting the spectroscopic properties of natural (and nature-inspired) dyes and pigments.

Resumo em Inglês:

Genome mining provides exciting opportunities for the discovery of natural products. However, in contrast to traditional bioassay-guided approaches, challenges of genome mining include poor or no expression of biosynthetic gene clusters (BGCs). Additionally, given that thousands of BGCs are now available through extensive genome sequencing, how does one select BGCs for discovery? Synthetic biology techniques can be used for BGC refactoring and activation, whereas resistance-gene-directed genome mining is a promising approach to discover bioactive natural products. Here we report the selection of a BGC by applying a resistance-gene-directed approach, cloning of the silent BGC from Micromonospora sp. B006, promoter exchange, and heterologous expression in Streptomyces coelicolor M1152. While we have yet to identify the encoded compound, we unexpectedly observed induction of a host metabolite, which we hypothesize is due to the presence of a caseinolytic protease C (ClpC) chaperone gene in the BGC, suggesting that ClpC chaperones may be used for BGC activation.

Resumo em Inglês:

A series of four water-soluble benzazole dyes that emit fluorescence by the excited state intramolecular proton transfer (ESIPT) mechanism were structurally characterized by Fourier transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic resonance (NMR) attached proton test (APT) and mass spectrometry. Their photophysical properties were systematically studied by UV-absorption and fluorescence emission. Some photophysical parameters were obtained by semi-empirical PM3 and ZINDO methods, and related to experimental photophysical data. Changes in the absorption and fluorescence emission spectra as well as conformational equilibrium between different species were investigated in solvents of different polarities and under different pH conditions. These benzazole dyes emit dual fluorescence emission in the blue-orange region with a Stokes shift between 2617-12337 cm-1. In general, these dyes are potentially interesting for studies of biological systems in an aqueous environment due to the presence of groups that increase aqueous solubility and reactivity with biomolecules. The present dyes were successfully used as new probes by means of direct staining of larvae. The obtained results indicate that these fluorescent dyes permit a quick, easy and selective visualization of larvae.

Resumo em Inglês:

A new compound named methyl (6S,7S,2E,4E)-6,7-dihydroxy-4,6-dimethyl octanoate was isolated from Saccharicola sp. using high performance liquid chromatography-solid phase extraction-transfer tube (HPLC-SPE-TT), together with four known compounds, fusaric acid, trans-4-hydroxymellein, thymidine and adenosine. Saccharicola sp. was isolated from the stems of Eugenia jambolana Lam. (Myrtaceae) as endophytic fungus. The structure of this novel substance was established based on its spectroscopic data, including 1H and 13C nuclear magnetic resonance (NMR), 2D NMR techniques and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). This paper deals with the first report of its kind on this compound in Saccharicola sp.

Resumo em Inglês:

Intrigued by the recent discovery of caramboxin by Brazilian researchers, we present the results from our studies toward the racemic synthesis of caramboxin analogs through the ortho-carboxylation of 3,5-dimethoxy benzyl derivatives. Three different approaches were tested, and the route involving a Vilsmeier-Haack formylation followed by a Lindgren oxidation provide a potential intermediate for the synthesis of several caramboxin analogs.

Resumo em Inglês:

In the present investigation, a collection of twenty two nerol derivatives, containing 1,2,3-triazolic appendages, was synthesized and screened in vitro for their cytotoxic activity against HL60, Nalm6, and Jurkat human leukemia cells as well as against B16F10 (melanoma cell line). In most cases, derivatives were able to reduce cell viability. The most potent compound (Z)-4-(((3,7-dimethylocta-2,6-dien-1-yl)oxy)methyl)-1-(4-(trifluoromethoxy)benzyl)-1H-1,2,3 triazole showed antiproliferative activity against Jurkat cells and reduced B16F10 cell migration. Physicochemical properties of the compounds were calculated in order to evaluate their potential for drug development. Most of the evaluated physicochemical parameters seemed to be favorable for drug development. In addition, for a better understanding of the biological activity results, 3D quantitative structure-activity relationship (QSAR) studies were carried out. 3D-QSAR studies indicate that the anticancer activities observed for the cell lines HL60 and Jurkat may occur by a similar mechanism of action and the same was found for the Nalm6 and B16F10 cell lines.

Resumo em Inglês:

The conventional biodiesel process, although it reaches high conversion yields and productivity, faces problems related to the use of homogeneous catalysts. This work aims to study mixtures of calcium oxide (CaO) and niobium oxide (Nb2O5) as the heterogeneous catalyst. It was used a full 23 factorial design with four central points to analyze how the mass percentage of the oxides, the molar ratio of reactants, and the reaction temperature affect the conversion yield to methyl esters. The best conversion yield was found near to 89% using 1.8% of catalyst, a 1:36 oil to methanol ratio and at 77 ºC as reaction temperature. Finally, it was performed a simplified simulation to compare the heterogeneous catalyst process with the conventional process, and an algorithm to compare the effects of the exit streams of each process would have on the environment. The simulations results display a better performance for the heterogeneous catalyst process studied.

Resumo em Inglês:

In this article density functional theory (DFT)-based calculations were employed to investigate the electrochemistry of the antitumor ruthenium complexes trans-tetrachloro(dimethylsulfoxide)imidazole ruthenate(III) (NAMI-A) and trans-[tetrachlorobis(1.-indazole)ruthenate(III)] (KP1019), their hydrolysis products as well as their interactions with biological S-donors and N-donors targets as cysteine, glutathione and guanine nucleobase. The compounds exhibit different electrochemical behavior upon hydrolysis. While the reduction potential of NAMI-A increases up to 0.8 V upon hydrolysis, the reduction potential of KP1019 remains almost constant after the first hydrolysis. NAMI-A and KP1019 complexes have thermodynamic preference to be reduced prior to undergoing hydrolysis and, strong preference to undergo successive hydrolysis instead of interacting with the S-donor and N-donor ligands. Interaction with S-donor ligands in the unprotonated form is highly unfavorable, with the free energy in solution (ΔGsol) ≥ 18 kcal mol-1. For both complexes, the interaction with the guanine and glutathione are of the same magnitude (ΔGsol ca. –0.6 kcal mol-1) meaning that these ligands can compete for binding to the metallodrug.

Resumo em Inglês:

The stereoselective total synthesis of (+)-epi-cytoxazone was performed satisfactorily in 8 steps, in 17% overall yield, via a novel route from 2,3-O-(3-pentylidene)-(R)-glyceraldehyde. The bulky group alkene-ketal allowed intramolecular control of the target molecule's asymmetric centers in the dihydroxylation step by promoting the approach of OsO4 to the face opposite to that of the ketal group.

Resumo em Inglês:

Leishmaniasis is a neglected infectious disease caused by different species of the Leishmania parasite and is one of the major public health problems in developing countries. Despite the progress in fundamental knowledge about the Leishmania parasite, current therapy against leishmaniasis is still unsatisfactory due to limited efficacy, prolonged treatment, high cost and undesirable adverse effects. Thus, the research for new prototypes compounds of antileishmaniasis drugs remains a matter of current importance. The objective of this study was to evaluate the leishmanicidal activity of cytochalasin B, a natural compound isolated by our group in a previous study, against L. amazonensis, using experimental tests and computational simulation methodologies. The results of the biological evaluation showed that cytochalasin B has antileishmanial activity against the promastigote form of Leishmania amazonensis. These results are corroborated by the docking and molecular dynamics that showed that the activity occurs due to the inactivation of the trypanothione reductase enzyme (TryR).

Resumo em Inglês:

This paper reports the DNA interaction and cytotoxicity of binary and ternary copper(II) complexes of valproic acid with phenanthroline or bipyridine and the complementary characterization of Cu(Valp)2Bipy by crystallography. Circular dichroism, plasmid and oligonucleotide assays have shown that the complexes interact with DNA in different manners and are able to cleave plasmid DNA and oligonucleotides at concentrations from 10 to 1000 mol L-1. The plasmid DNA cleavage is enhanced 650, 375 and 285 times by photo activation with UVB light for the complexes Cu(Valp)2Phen, Cu(Valp)2Bipy and Cu2(Valp)4, respectively. Cytotoxicity assays demonstrated that V79 cells were more sensitive to CuII derivatives than sodium valproate as evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) and clonogenic assays, where the cytotoxic profile of the compounds was: Cu(Valp)2Phen higher than Cu(Valp)2Bipy, higher than Cu2(Valp)4. Therefore, we report two copper complexes, which interact with DNA and promote its cleavage, leading to an enhanced cytotoxicity when compared to valproic acid.

Resumo em Inglês:

Emerging contaminants have been considered one of the main concerns for ensuring the quality of water around the world. This work presents the results of 10 years of analyses carried out in the state of São Paulo (Brazil) that has the high population density and intense agricultural and industrial activities. In this work 58 compounds (9 hormones, 14 pharmaceuticals and personal care products, 8 industrial compounds, 17 pesticides and 10 illicit drugs) were determined from 2006 to 2015 in 708 samples including raw and treated sewage, surface and ground and drinking waters. A preliminary risk assessment for aquatic life protection identified potential risks for caffeine, paracetamol, diclofenac, 17α-ethynylestradiol, 17β-estradiol, estriol, estrone, testosterone, triclosan, 4-n-nonylphenol, bisphenol A, atrazine, azoxystrobin, carbendazim, fipronil, imidacloprid, malathion and tebuconazole. Drinking water criteria were available only for 22 compounds and for them no adverse effects were expected at the concentrations found, except for 17β-estradiol.

Resumo em Inglês:

Microalgae lipid-derived biofuels is considered promising candidates for substitution of petroleum-based energy sources. However, the lipid extraction from the algal biomass stands as a challenge due to its low yields and cost-intensive cell disruption procedures. In this study a multivariate optimization of the extraction conditions was suggested, aiming a maximization of the lipid extraction from Scenedesmus sp. microalgae grown using wastewater as a nutrient medium. The extraction method, extraction time, solvent mixture and pretreatment were considered between upper and lower levels in order to access their significance, including their interactions, on the experimental response, while using a reduced number of experiments. The studies were performed using low-cost extraction methods (magnetic stirring and ultrasonication). The optimal extraction condition was obtained using CHCl3:MeOH (2:1) solvent mixture, in a 2-hour extraction period using ultrasonication. Fatty acid profiles of extracted lipids were also evaluated.

Resumo em Inglês:

Montmorillonites modified with lanthanum(III) and iron(III) were prepared from two commercial clays. These materials were characterized by powder X-ray diffraction analysis, X-ray fluorescence, infrared spectroscopy, N2 adsorption, and scanning electron microscopy. The incorporation of lanthanum(III) and iron(III) varied from 0 to 4.00%. The amount of these cations governed the adsorption capacity of the material since an increase in the percentage of La by 1.7 times improved the adsorption capacity by 3.3 times. The structural properties of the precursor clay minerals, such as pore size, may have influenced the extension of the modification process. Kinetics and equilibrium studies indicated that adsorption occurs mainly within 24 h, and the pseudo-second order and Lagmuir models described the process. The phosphate adsorption capacity ranged from 2.86 to 17.86 mg g-1 for the modified materials and was mainly dependent on the La content. A laboratory test with a natural water sample from the Jacarepaguá Lagoon showed reduction of the soluble reactive phosphorus concentration from 0.41 to 0.04 mg L-1, for the material with 4.00% La2O3. The materials described in this work were effective for the reduction of the soluble reactive phosphate, contributing to the research of a national product destined to the restoration of eutrophic aquatic environments.

Resumo em Inglês:

Electrochemical methods are powerful in the characterization and design of redox-modulating agents. We, herein, report the electrochemical investigation, in aprotic medium, of eleven synthetic 3-thio-substituted-nor-beta-lapachones, along with the determination of cytotoxic activity and correspondent selectivity index, against several cancer cell lines and one normal cell. Four of the quinones are novel compounds. The redox behavior is representative of two independent systems: the easy reduction of the quinone moiety and, at far more negative potential, the reductive cleavage of the C-S-C bonding; and the anodic part controlled by the oxidation of the sulfur moiety. The compounds have shown relevant cytotoxic activity, with emphasis on 3-phenyl-thio-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione (compound 2), which mechanism of molecular action was shown to be related to reactive oxygen species (ROS) release. Despite the absence of a linear correlation, there is a trend: the majority of the thionaphthoquinones, with values of first wave reduction potential, less negative than -0.65 V, were active. The less electrophilic compound (3-(cyclohexylthio)-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione, cyclohexyl derivative) is also the less cytotoxic toward cancer cells. Agents containing chalcogens and quinones can be used to attack entities with a disturbed redox balance.

Resumo em Inglês:

The genus Streptomyces represents one of the largest producers of molecules with antibiotic activity. The whole genome sequencing of the endophytic microorganism Streptomyces sp. CBMAI 2042 revealed 35 gene clusters encoding for secondary metabolism including 3 non-ribosomal peptide synthetases (NRPS) and 7 NRPS-hybrids. Combining genome mining and cultivation profile analysis, the depsipeptide ionophore valinomycin was identified as one of the main metabolites produced by this strain. To better understand the metabolic machinery codified in CBMAI 2042 genome an adenylation domain from a hybrid NRPS cluster was deleted through a double crossing knockout experiment. Though the deletion was not plentiful to elucidate the encoded NRP metabolite related to the adenilation domain, an astounding increase of 10.5-fold in valinomycin production was observed in the mutant. These results suggest a metabolic flux redistribution of common substrates as an outcome of a gene target deletion.