An experimental and theoretical approach on oxidative metabolism of paracetamol was applied for the pharmaceutical chemistry learning. Classical reactions, functional group identification, structural parameter, and chemical reactivity using frontier orbitals and Fukui index were used explaining the main products between N-acetyl-p-benzosemiquinone (NAPQI) and thiolic compounds. The chemoprotection mechanisms by N-acetyl-cysteine on high dosage of paracetamol are consistent with theoretical and experimental results. The methods also described the relationship between the chemical reactivity of quinone-imine system and the induced-toxicity of paracetamol by Michael reaction. These results can be applied in experimental pharmaceutical chemistry teaching.

According to the World Health Organization (WHO), Chagas disease (CD), whose etiological agent is the Trypanosoma cruzi (T. cruzi) parasite, affects about eight million people, mainly in Latin America. The cruzain enzyme is highlighted among the main biological targets, since it is the most abundant of the cysteine protease class from T. cruzi and is involved in the entire life cycle of the parasite, essential in regulating the interaction between parasite and host. The drugs available for the treatment of CD usually have strong side effects, and the nitro(triazole/imidazole)-based heteroarylamide/sulfonamide compounds (HA/S) emerge with high antitrypanosomal potential. In this study, the quantitative structure-activity relationship (QSAR) were built using partial least squares (PLS) regression, and the results were robust and adequate for predicting and proposing five new derivatives according to the statistical parameters. The docking results suggest that the best-scored HA/S derivatives showed hydrogen bonds with the residuals that comprise the catalytic region of the enzyme. The molecular dynamics (MD) simulations, performed with different methods, revealed the strong stability of the compound obtained by the QSAR model of this study, in addition to a better binding free energy value than the HA/S obtained from literature.

Ferulic acid (FERH) is known to exert leishmanicidal action against Leishmania (Leishmania) amazonensis. In this study, the ferulate anion (FER–) was intercalated into a layered double hydroxide (LDH) for FER– delivery during an antileishmania in vitro test. The LDH-FER– intercalation compound was prepared by coprecipitation and was characterized by X-ray powder diffraction, thermogravimetry, UV-Vis, infrared, and Raman spectroscopy analyses. Leishmania (L.) amazonensisin vitro assays were conducted to assess the LDH-FER– potential. LDH-FER– was found to promote a dose-dependent reduction of L. (L.) amazonensis amastigotes (intracellular form, half maximal inhibitory concentration (IC50) = 1.78 µg mL-1) without exerting a deleterious effect on the host macrophages (medium cytotoxic concentration (CC50) = 212.61 µg mL-1 and selectivity index = 119.4). LDH-FER– was found to be an effective inhibitor of the amastigote form of L. (L.) amazonensis, suggesting that LDH-FER– was able to deliver FER– inside the parasitophorous vacuoles where the pH is more acidic.

Neolignans are a class of natural products with a wide range of biological effects. These substances are of great synthetic and biological interest, especially in searching for novel anticancer agents. In this paper, we report the synthesis of a new subclass of 8,4’-oxyneolignan analogues (β-ketoethers and β-ketoesters) and their cell viability assay on twenty four different cancer cells, among leukemias and carcinomas. Three compounds inhibited the growth of most human cancer cells. 2-Oxo-2-phenylethyl(2E)-3-[4-(2-oxo-2-phenylethoxy) phenyl]prop-2-enoate showed an antiproliferative activity superior to doxorubicin for U-87, U-138 MG and H1299 cell types and (E)-2-oxo-2-phenylethyl 3-(3-methoxy-4-(2-oxo-2-phenylethoxy)phenyl)acrylate was found to be very selective, demonstrating a growth inhibition of 92.0% against KG-1 cells. Furthermore, 1-oxo-1-phenylpropan-2-yl cinnamate exhibited significant inhibition activity in a range of 52.2 to 91.2% against twelve kinds of leukemia cell lines, revealing excellent results and very comparable to the reference drug.

Due to the economic potential of camu-camu, considering its high concentration of vitamin C, the aim of this work was to evaluate the quality and genetic variability seven accessions of camu-camu conserved in genebank (BAG) of Embrapa Amazônia Oriental, in the state of Pará, Amazon region, Brazil. The fruits of camucamuzeiro were analyzed for physicochemical characterization (standard methodologies) and mineral composition. The data were subjected to multivariate statistical analysis, using the techniques of cluster analysis and principal component analysis. The formation of different groups for each genotype, which shows the genetic variability and the dissimilarity of the genotypes in the species data, may be used to guide the selection of promising genotypes to enrich the programs of genetic improvement of the camucamuzeiro. Ascorbic acid showed levels above 1000 mg 100 g-1, however, genotypes 4, 1 and 2 show the highest potential and the most promising nutritional capacity, but genotype 4 showed good characteristics for the moisture, acidity, carbohydrates, Cu and Zn and differs totally from others about the total soluble solids (TSS) and flavon-3-ol, features that make it the most promising genotype. It was possible to separate the seven different genotypes using multivariate analysis (hierarchical cluster analysis-HCA and principal component analysis-PCA).

<p>Labdane diterpenes exhibit important bioactivities such as cardiovascular effects in rats as well as effects in the treatment of autoimmune diseases and Alzheimer syndrome. Recently, the labdane diterpenes <italic>ent</italic>-13-<italic>epi</italic>-manoil oxide, ribenone and ribenol were isolated from <italic>Croton palanostigma</italic>. The computational method DFT/B3LYP/cc-pVDZ was used to optimize the structures of these diterpenes and to calculate infrared data. Chemical shifts (δ_H and δ_C) of the minimum energy structures (local minimum) were calculated and compared with the experimental data. Comparison of the NMR data by simple linear regression (SLR) showed satisfactory statistical results with a correlation coefficient (R²) and predictive ability (Q²) of over 98%. The predicted NMR data were used to confirm the δ_H values that have not been published.</p>

Vinte e sete amostras de mel, produzidas em dez cidades do Estado do Pará (Região Amazônica, norte do Brasil) por três espécies diferentes de abelhas (Apis mellifera, Melipona fasciculata e Melipona flavoneata), foram analisadas em seus teores de elementos minerais (Al, As, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Ni, Sr e Zn) e alguns parâmetros fisicoquímicos (cor, umidade, densidade, pH, sólidos insolúveis e solúveis totais, cinzas, condutividade elétrica, índice de formol, acidez livre, hidroximetilfurfural, açúcares redutores e totais e sacarose). Os teores minerais foram determinados via espectrometria de emissão atômica por plasma acoplado indutivamente (ICP OES) e as análises dos parâmetros físico-químicos seguiram metodologias oficiais. Os resultados das análises físico-químicas apresentaram-se de acordo com a legislação nacional e internacional, bem como com outros trabalhos similares ao redor do mundo. A análise estatística multivariada (análise por agrupamento hierárquico (HCA) e por componentes principais (PCA)) foi aplicada aos resultados dos teores metálicos e aos parâmetros físico-químicos, sendo possível a separação das amostras de mel conforme a espécie produtora.

Twenty seven samples of honey produced in ten cities of Pará State (Amazon region, North of Brazil) by three different species of bee (Apis mellifera, Melipona fasciculata and Melipona flavoneata) were characterized based on mineral composition (Al, As, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Ni, Sr and Zn), and some physicochemical parameters, namely color, moisture, density, pH, total soluble solids, insoluble solids, ash, electrical conductivity, formol index, free acidity, hydroxymethylfurfural, reducing sugars, total sugars and sucrose. The mineral content was determined using inductively coupled plasma-optical emission spectrometry (ICP OES), and the physicochemical parameters were determined according to officially approved methods. The results of the physicochemical analysis were in agreement with national and international regulations, and with the results of similar studies from around the world. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were applied in the study of the results of the mineral contents and physicochemical parameters, and it was possible to distinguish the honey samples produced by each of the three different species of bee.

No ano de 2007, águas superficiais foram coletadas a partir de 21 pontos de amostragem na cidade de Barcarena, Região Norte, Brasil: um ponto de amostragem localizado em um pequeno córrego que recebe descarga de resíduos a partir da indústria de beneficiamento do caulim e deságua no Rio Curuperê, três pontos de amostragens localizados próximos de fontes que emergem na margem esquerda e deságuam no Rio Curuperê, nove pontos de amostragem no Rio Curuperê, que deságua no Rio Dendê, e oito no Rio Dendê, afluente da margem esquerda do Rio Pará. Para todas as amostras de água foram quantificadas 14 variáveis físico-químicas e níveis de 12 metais. Os resultados nos pontos próximos das fontes do Rio Curuperê apresentaram perfil físico-químico e níveis de metais típicos para águas superficiais e esses valores foram utilizados como referência para comparar e identificar possíveis alterações nas características químicas para os demais pontos de amostragem. Quando os resultados das fontes do rio Curuperê foram comparados com os resultados do ponto próximo a descarga de resíduos industriais foram observadas fortes alterações nos valores de 6 variáveis físico-químicas (pH, condutividade elétrica (EC), total de sólidos suspensos (TDS), nitrogênio amoniacal (N-NH4), sulfato (SO4) e salinidade) e aumento em magnitude dos níveis de quatro metais (Al, Fe, Mn e Zn), caracterizando que esses resíduos eram descarregados no ambiente sem tratamentos adequados. Os resultados nos demais pontos de amostragem demonstraram que estas condições anômalas também foram encontradas ao longo dos Rios Curuperê e Dendê, principalmente durante a maré baixa. A partir desta caracterização química das águas foram identificadas condições prejudiciais aos ecossistemas aquáticos e potencial risco à saúde da população local que usa os rios para consumo, recreação e transporte.

In 2007, surface waters were collected from 21 sampling points in Barcarena City in Northern Region of Brazil: one sampling point located in a stream that receives discharge of wastewater from a kaolin processing industry and flows into the Curuperê River, three sampling points located near sources that emerge on the left bank and flow into the Curuperê River, nine sampling points in Curuperê River, which flows into the Dendê River, and eight in Dendê River, a tributary on the right bank of the Pará River. For all water samples were quantified 14 physicochemical variables and levels of 12 metals. The results in the points near the sources of the Curuperê River presented physicochemical profile and metal levels which are typical of surface waters being used as reference to compare and identify possible changes in the chemical characteristics of the other sampling points. The comparison between the results obtained for the sources of the Curuperê River and the ones for the point near the discharge of industrial wastewater revealed strong changes in the values of 6 physicochemical variables (pH, electrical conductivity (EC), total dissolved solids (TDS), sulfate (SO4), ammoniacal nitrogen (NH4-N) and salinity) and an increase in magnitude of the levels of four metals (Al, Fe, Mn and Zn). These facts characterized that the wastewaters were discharged into the environment without adequate treatment. Results in other sampling sites showed that these anomalous conditions were also found along the Curuperê and Dendê Rivers, especially during low tide. This chemical characterization of the waters allowed to identify harmful conditions to aquatic ecosystems and potential health risk for the local people, who use the rivers for drinking water, recreation and transportation.

O fungo Aspergillus flavus isolado como endofítico da planta Paspalum maritimum Trin. foi avaliado quanto ao seu potencial de aplicação em reações de biotransformações. Os compostos chalcona (1), 3,4,5-trimetoxichalcona (2) e 2,3,4,4'-tetrametoxichalcona (3) foram biotransformados, respectivamente, na diidrochalcona (4), 3,4,5-trimetoxidiidrochalcona (5) e 2,3,4,4'-tetrametoxidiidrochalcona (6). As estruturas destes compostos foram determinadas por análises de RMN uni e bidimensionais e por espectrometria de massas. As diidrochalconas 5 e 6 são substâncias inéditas.

The fungus Aspergillus flavus isolated as endophytic of the plant Paspalum maritimum Trin. was evaluated for its potential application in biotransformation reactions. The compounds chalcone (1), 3,4,5-trimethoxychalcone (2) and 2,3,4,4'-tetramethoxychalcone (3) were biotransformed, respectively, in dihydrochalcone (4), 3,4,5-trimethoxydihydrochalcone (5) and 2,3,4,4'-tetramethoxydihydrochalcone (6). The structures were elucidated by spectroscopic methods including 1D and 2D NMR techniques, and MS analysis. The dihydrochalcones 5 and 6 are new compounds.

Foram investigadas a hidrólise da sacarose e a preferência pela glicose frente à frutose no processo de produção do 5-hidroxi-2-hidroximetil-γ-pirona (HHMP) na presença de Aspergillus flavus IOC 3974 cultivado em meio líquido Czapeck. Quantidades de 0,5g de pelletes foram utilizadas como inóculo. Doze frascos cônicos de 250 ml contendo 100 ml de meio de culturacom diferentes concentrações de sacarose foram utilizados.Os microrganismos foram cultivados a 120 rpm e 28"C por 16 dias sem ajuste do pH. O maior rendimento do HHMP foi 26g l-1em 120g l-1de sacarose. Nestas condições, A. flavus, foi capaz de produzir uma invertase possibilitando a hidrólise de 65% da concentração total de sacarose em 24 horas, conjuntamente com a produção de uma isomerase que foi capaz de converter a frutose em glicose. Este trabalho está focalizado preferencialmente no consumo da glicose frente à frutose por A. flavus e na estratégia de produção do HHMP.

The sucrose hydrolysis and the preference of consumption of glucose instead of fructose were investigated for the production of 5-hydroxy-2-hydroxymethyl-γ-pyrone (HHMP) in the presence of Aspergillus flavus IOC 3974 cultivated in liquid Czapeck medium. Standardized 0.5g of pellets were transferred as inoculum into twelve conical flasks of 250 ml containing 100 ml of medium with different sucrose concentration, which was kept at 120 rpm and 28"C for 16 days without pH adjustment. Aliquots of 500μl of the broth culture were withdrawn at 24 h intervals and analyzed. The major yield of HHMP was 26g l-1 in 120g l-1 of sucrose. At these conditions, A. flavus produced an invertase capable of hydrolyzing 65% of total sucrose concentration in 24h, and an isomerase capable of converting fructose into glucose. In this work, it focused the preference for glucose and, then, of fructose by A. flavus and the strategy used to produce HHMP.

Estudos fitoquímicos com as cascas do caule e com as folhas de Croton palanostigma Klotzsch (Euphorbiaceae) levaram ao isolamento do novo diterpeno clerodânico 8-epicordatina (2), além de éster metílico do ácido 12-oxohardwickiico (3), aparisthmano, cordatina (1), ácido ent-trachiloban-18-óico, óxido de ent-13-epimanoila, óxido de ent-3-oxo-13-epimanoila, óxido de ent-3β-hidroxi-13-epimanoila, sitosterol, estigmasterol, estigmastan-3-ona, 6β-hidroxiestigmast-4-en-3-ona, 6β-hidroxiestigmasta-4,22-dien-3-ona, estigmast-4-en-3-ona, estigmasta-4,22-dien-3-ona, ácido 3-O-acetilaleuritolico, 11α-hidroxiurs-12-en-3-ona, α-amirenona, 24-metilenocicloartenona e lupenona. Estas substâncias foram isoladas através de procedimentos fitoquímicos usuais e suas estruturas foram deduzidas por estudos espectroscópicos, incluindo experimentos em 2D. Adicionalmente, a estrutura cristalina de 8-epicordatina (2) foi determinada por difração de raios-X. Cálculos teóricos de RMN ao nível B3PW91/DGDZVP foram usados para confirmação dos assinalamentos dos deslocamentos químicos dos hidrogênios H-7α e H-7β de 8-epicordatina.

Phytochemical studies of the bark and leaves of Croton palanostigma Klotzsch (Euphorbiaceae) led to the isolation of a new clerodane diterpene, 8-epicordatin (2), in addition to 12-oxohardwickiic acid methyl ester (3), aparisthman, cordatin (1), ent-trachyloban-18-oic acid, ent-13-epimanoyl oxide, ent-3-oxo-13-epimanoyl oxide, ent-3β-hydroxy-13-epimanoyl oxide, sitosterol, stigmasterol, stigmastan-3-one, 6β-hydroxystigmast-4-en-3-one, 6β-hydroxystigmasta-4,22-dien-3-one, stigmast-4-en-3-one, stigmasta-4,22-dien-3-one, 3-O-acetylaleuritolic acid, 11α-hydroxyurs-12-en-3-one, α-amyrenone, 24-methylenecycloartenone and lupenone. These compounds were isolated using typical phytochemical procedures and the structures were deduced from spectroscopic studies, including 2D NMR experiments. In addition, the crystalline structure of 8-epicordatin (2) was determined by X-ray diffraction. NMR theoretical calculations at the B3PW91/DGDZVP level were used to confirm the assignment of the chemical shifts of the H-7α and H-7β hydrogens of 8-epicordatin.

A síntese e a estrutura cristalina por difração de raios-X de dois análogos de neolignanas, 2-(4-clorofenil)-1-feniletanona (20) e 2-[tio(4-clorofenil)]-1-(3,4-dimetoxifenil)propan-1-ona (12) são descritas. O composto 12 apresenta atividade intracelular contra Leishmania donovani e Leishmania amazonensis de amastigotas que causam a leishmaniose tegumentar e visceral. Além disso, a teoria do funcional de densidade (DFT) com o funcional híbrido B3LYP foi empregado para calcular um conjunto de descritores moleculares para dezenove análogos sintéticos de neolignanas com atividades antileishmaniose. Posteriormente, a análise discriminante stepwise foi realizada para investigar possíveis relações entre a estrutura molecular e atividades biológicas. Por meio dessa análise os compostos foram classificados em dois grupos ativos e inativos de acordo com seu grau de atividade biológica, e as propriedades mais importantes foram as cargas de alguns átomos, a afinidade eletrônica e o ClogP.

The synthesis and X-ray crystal diffraction structure of two analogues of neolignans, 2-(4-chlorophenyl)-1-phenylethanone (20) and 2-[(4-chlorophenyl)thio]-1-(3,4-dimethoxyphenyl)propan-1-one (12) is described. The compound 12 presents activity against intracellular Leishmania donovani and Leishmania amazonensis amastigotes that cause cutaneous and visceral leishmaniasis. In addition, the density functional theory (DFT) with the B3LYP hybrid functional was employed to calculate a set of molecular descriptors for nineteen synthetic analogues of neolignans with antileishmanial activities. Afterwards, the stepwise discriminant analysis was performed to investigate possible relationship between the molecular descriptors and biological activities. Through this analysis the compounds were classified into two groups active and inactive according to their degree of biological activities, and the more important properties were charges on some key atoms, electronic affinity and ClogP.

Amostras de cabelo foram utilizadas como bioindicador para avaliar os níveis de As, Cd, Pb e Hg na população residente na área "Volta Grande" do rio Xingu, no Norte do Brasil. As concentrações de As e Cd estão de acordo com os valores encontrados na literatura, no entanto, foram encontrados valores anômalos de Pb e Hg , o que pode sugerir uma variação inter-regional. Os elevados valores encontrados de Pb e Hg, em cabelos de moradores da Ilha do Canteiro, podem ser atribuídos à exposição ambiental das famílias, por estarem em uma área ambiental impactada pela mineração de ouro. A aplicação dos métodos de estatística multivariada mostrou que a concentração dos metais, estudados neste trabalho, pode ser classificatória entre pessoas de localidades diferentes do município de Altamira. Os resultados neste trabalho refletem o impacto ambiental destes elementos sobre a saúde dos habitantes desta área de garimpagem de ouro.

Human hair was used as a bioindicator to evaluate the levels of As, Cd, Pb and Hg in the resident population of the "Volta Grande" area of the Xingu river, in the North of Brazil. The concentrations of As and Cd are in agreement with the values found in the literature, however, the Pb and Hg concentration is very different, which can suggest an inter-regional variation. Moreover, the high values found for these elements in the residents of the Canteiro Island can be attributed to environmental exposure of this population in an area with environmental impact from activities of gold mining. The application of these methods showed that the concentrations of the metals studied in this work can correctly classify two different localities in the Altamira district. The results reflect the impact of these elements on the health of the inhabitants of this auriferous area.

Métodos quimiométricos (estatísticos) são empregados para classificar um conjunto de compostos derivados de neolignanas com atividade biológica contra a Paracoccidioides brasiliensis. O método AM1 (Austin Model 1) foi utilizado para calcular um conjunto de descritores moleculares (propriedades) para os compostos em estudo. A seguir, os descritores foram analisados utilizando os seguintes métodos de reconhecimento de padrões: Análise de Componentes Principais (PCA), Análise Hierárquica de Agrupamentos (HCA) e o método de K-vizinhos mais próximos (KNN). Os métodos PCA e HCA mostraram-se bastante eficientes para classificação dos compostos estudados em dois grupos (ativos e inativos). Três descritores moleculares foram responsáveis pela separação entre os compostos ativos e inativos: energia do orbital molecular mais alto ocupado (E HOMO), ordem de ligação entre os átomos C1'-R7 (L14) e ordem de ligação entre os átomos C5'-R6 (L22). Como as variáveis responsáveis pela separação entre compostos ativos e inativos são descritores eletrônicos, conclui-se que efeitos eletrônicos podem desempenhar um importante papel na interação entre receptor biológico e compostos derivados de neolignanas com atividade contra a Paracoccidioides brasiliensis.

Chemometric (statistical) methods are employed to classify a set of neolignan compounds with activity against Paracoccidioides brasiliensis. The AM1 (Austin Model 1) method was used to calculate a set of molecular descriptors (properties) of the neolignan compounds under study. The descriptors were further analyzed using Principal Components Analysis (PCA), Hierarchical Cluster Analysis (HCA) and K-Nearest Neighbor (KNN) chemometric methods. The PCA and HCA methods were quite efficient to classify the compounds into two groups (active and inactive) and three descriptors were found to be important in the classification: the highest occupied molecular orbital energy (E HOMO), the bond order between C1'-R7 atoms (L14) and the bond order between C5' -R6 atoms (L22). The three variables responsible for the separation between active and inactive compounds are all electronic descriptors, therefore we can conclude that electronic effects should have an important role when one is trying to understand the activity of neolignan compounds against Paracoccidioides brasiliensis.