Davi do Socorro Barros Brasil

Mercury levels assessment in hair of riverside inhabitants of the Tapajós River, Pará State, Amazon, Brazil: Fish consumption as a possible route of exposure

The study present evaluated the levels of mercury (Hg) and methylmercury (MeHg) in hair samples of people from Barreiras community, riverside inhabitants of the Tapajós River (Pará, Brazil), an area impacted by clandestine gold mining, as well as we analyzed the levels of Hg and Se (selenium) in nine fish species (carnivores and non-carnivorous) from the Tapajós River, which stand out as the main species consumed by riverside inhabitants, to evaluate a relationship between frequency of fish consumption and Hg concentration, and also to evaluate possible mechanisms of fish protection (or non-protection) to Hg exposure by Se. Furthermore we analyze the water quality to evaluate the environmental trophic state, fact responsible by creating conditions that can potentiate the effects of toxic mercury. Concentrations of Hg and MeHg were analyzed in hair samples of 141 volunteers in different age band. Of those, 84.40% of samples present values above the threshold for biological tolerance, which is 6.00μgg(-1) of total Hg in hair. Total Hg, in men there was a variation of 2.07-24.93μgg(-1), while for women the variation was 4.84-27.02μgg(-1). Consequently, the level of MeHg in men presented a variation of 1.49-19.57μgg(-1), with an average of 11.68μgg(-1), while with women the variation was from 3.73 to 22.35μgg(-1), with an average of 10.38μgg(-1). In fish species, Hg concentrations in carnivorous species had an average of 0.66μgg(-1), higher than that permitted by current legislation, ranging from 0.30 to 0.98μgg(-1), while the non-carnivorous species have values below the recommended by the legislation averaging 0.09μgg(-1), ranging between 0.02 and 0.44μgg(-1). For Se in fish, show that among carnivores, the contents of Se ranged between 0.18 and 0.54μgg(-1) with a mean of 0.34μgg(-1), while for non-carnivores these values were of the order of 0.16-0.56μgg(-1), with an average of 0.32μgg(-1). In surface water quality variables at the sampling points all showed values in accordance with the range established by current legislation. In this regard, the results provided by this study, while not conclusive, are strong indicators that despite not having been shown the relationship between the concentration of mercury in hair and feeding habits along the Tapajós River basin communities showed that a plausible correlation exists between levels of mercury and selenium in fish. This fact may serve as a subsidy to research human health, because in the Amazon, there is still a lot to examine with regards to the full understanding of the Se cycle.

A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity

The Density Functional Theory (DFT) method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS) and principal component regression (PCR) models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R2 = ±0.0106, R2ajust = ±0.0125, s = ±0.0234, F(4,11) = ±12.7802, Q2 = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and SPRESS = ±0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set) with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA), cellular permeability (PCaCO2), cell permeability Maden Darby Canine Kidney (PMDCK), skin permeability (PSkin), plasma protein binding (PPB) and penetration of the blood-brain barrier (CBrain/Blood), and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.

Combined Kinetic Studies and Computational Analysis on Kojic Acid Analogs as Tyrosinase Inhibitors

Tyrosinase is a key enzyme in melanin synthesis and widely distributed in plants and animals tissues. In mammals, this enzyme is related to pigment production, involved in wound healing, primary immune response and it can also contribute to catecholamines synthesis in the brain. Consequently, tyrosinase enzyme represents an attractive and selective target in the field of the medicine, cosmetics and bio-insecticides. In this paper, experimental kinetics and computational analysis were used to study the inhibition of tyrosinase by analogs of Kojic acid. The main interactions occurring between inhibitors-tyrosinase complexes and the influence of divalent cation (Cu2+) in enzymatic inhibition were investigated by using molecular docking, molecular dynamic simulations and electrostatic binding free energy by using the Linear Interaction Energy (LIE) method. The results showed that the electrostatic binding free energy are correlated with values of constant inhibition (r2 = 0.97).Thus, the model obtained here could contribute to future studies of this important system and, therefore, eventually facilitate development of tyrosinase inhibitors.

Essential oil composition of Croton palanostigma Klotzsch from north Brazil

Os oleos essenciais das folhas, ramos finos, galhos, cascas do caule e frutos de Croton palanostigma foram analisados por CG e CG-EM. Os componentes principais determinados no oleo das folhas foram linalol (25,4%), (E)-cariofileno (21,0%), metileugenol (17,2%) e β-elemeno (6,0%); no oleo dos ramos finos foram α-pineno (41,4%), limoneno (29,0%), sabineno (11,5%) e β-pineno (5,7%); no oleo dos galhos foram metileugenol (24,1%), (E)-metilisoeugenol (15,3%), α-pineno (11,2%) e (E)-cariofileno (8,5%); no oleo das cascas do caule foram a-pineno (31,6%), metileugenol (25,6%) e (E)-metilisoeugenol (23,7%); e no oleo dos frutos foram linalol (42,7%), metileugenol (16,3%) e β-elemeno (6,4%). Analise estatistica mostrou que as folhas e os frutos apresentam significante similaridade entre si, assim como os galhos e as cascas do caule. Adicionalmente, o oleo obtido das cascas do caule possui elevada atividade larvicida sobre Artemia salina (CL50, 3,71 ± 0,01 mg mL-1).

Isolation, X-ray Crystal Structure and Theoretical Calculations of the New Compound 8-Epicordatin and Identification of others Terpenes and Steroids from the Bark and Leaves of Croton palanostigma Klotzsch

Estudos fitoquimicos com as cascas do caule e com as folhas de Croton palanostigma Klotzsch (Euphorbiaceae) levaram ao isolamento do novo diterpeno clerodânico 8-epicordatina (2), alem de ester metilico do acido 12-oxohardwickiico (3), aparisthmano, cordatina (1), acido ent-trachiloban-18-oico, oxido de ent-13-epimanoila, oxido de ent-3-oxo-13-epimanoila, oxido 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, acido 3-O-acetilaleuritolico, 11α-hidroxiurs-12-en-3-ona, α-amirenona, 24-metilenocicloartenona e lupenona. Estas substâncias foram isoladas atraves de procedimentos fitoquimicos usuais e suas estruturas foram deduzidas por estudos espectroscopicos, incluindo experimentos em 2D. Adicionalmente, a estrutura cristalina de 8-epicordatina (2) foi determinada por difracao de raios-X. Calculos teoricos de RMN ao nivel B3PW91/DGDZVP foram usados para confirmacao dos assinalamentos dos deslocamentos quimicos dos hidrogenios H-7α e H-7β de 8-epicordatina.

Volatiles, A Glutarimide Alkaloid and Antimicrobial Effects of Croton pullei (Euphorbiaceae)

Chemical investigation of Croton pullei (Euphorbiaceae) collected in the Brazilian Amazon region was revisited. The chemical composition of the essential oils of leaves and stems was analyzed by GC/MS. It was found that both the oils comprise mainly terpenes, among which linalool was the major one (24.90 and 39.72%, respectively). Phytochemical investigation of the stem methanol extract led to the isolation of a new natural product from the glutarimide alkaloid group named N-[2,6-dioxo-1-(2-phenylethyl)-3-piperidinyl]-acetamide, confirming that C. pullei is a rich source of this class of alkaloids. The hexane and methanol extracts of the stems of C. pullei showed moderate antibacterial and antifungal activity and the highest inhibition was observed when the methanol extract was tested against Staphylococcus aureus CCMB 262 and CCMB 263.

Identification of Novel Protein Kinase Receptor Type 2 Inhibitors Using Pharmacophore and Structure-Based Virtual Screening

The Protein Kinase Receptor type 2 (RIPK2) plays an important role in the pathogenesis of inflammatory diseases; it signals downstream of the NOD1 and NOD2 intracellular sensors and promotes a productive inflammatory response. However, excessive NOD2 signaling has been associated with various diseases, including sarcoidosis and inflammatory arthritis; the pharmacological inhibition of RIPK2 is an affinity strategy that demonstrates an increased expression of pro-inflammatory secretion activity. In this study, a pharmacophoric model based on the crystallographic pose of ponatinib, a potent RIPK2 inhibitor, and 30 other ones selected from the BindingDB repository database, was built. Compounds were selected based on the available ZINC compounds database and in silico predictions of their pharmacokinetic, toxicity and potential biological activity. Molecular docking was performed to identify the probable interactions of the compounds as well as their binding affinity with RIPK2. The compounds were analyzed to ponatinib and WEHI-345, which also used as a control. At least one of the compounds exhibited suitable pharmacokinetic properties, low toxicity and an interesting binding affinity and high fitness compared with the crystallographic pose of WEHI-345 in complex with RIPK2. This compound also possessed suitable synthetic accessibility, rendering it a potential and very promising RIPK2 inhibitor to be further investigated in regards to different diseases, particularly inflammatory ones.

Virtual Screening and Statistical Analysis in the Design of New Caffeine Analogues Molecules with Potential Epithelial Anticancer Activity

About 132 thousand cases of melanoma (more severe type of skin cancer) were registered in 2014 according to the World Health Organization. This type of cancer significantly affects the quality of life of individuals. Caffeine has shown potential inhibitory effect against epithelial cancer. In this study, it was proposed to obtain new caffeine-based molecules with potential epithelial anticancer activity. For this, a training set of 21 molecules was used for pharmacophore perception procedures. Multiple linear regression analyses were used to propose mono-, bi-, tri-, and tetra-parametric models applied in the prediction of the activity. The generated pharmacophore was used to select 350 molecules available at the ZINCpharmer server, followed by reduction to 24 molecules, after selection using the Tanimoto index, yielding 10 molecules after final selection by predicted activity values > 1.5229. These ten mole-cules had better pharmacokinetic properties than the other ones used as reference and within the clinical-ly significant limits. Only two molecules show minor hits of toxicity and were submitted to molecular docking procedures, showing BFE (binding free energy) values lower than the reference values. Statisti-cal analyses indicated strong negative correlations between BFE and pharmacophoric properties (high influence on BFE lowering) and practically null correlation between BFE and BBB. The two most prom-ising molecules can be indicated as candidates for further in vitro and in vivo analyzes.

Ricinine and other constituents of Aparisthmium cordatum (Euphorbiaceae)

The chemical study of Aparisthmium cordatum (Euphorbiaceae) led to the isolation of tannins, together with the alkaloid ricinine and other common compounds. The composition of A. cordatum is similar to most of the Alchornea species, from the same subtribe, except for the occurrence of ricinine. This study rectifies the first investigations published for A. cordatum that were conducted with Croton palanostigma. †This article is a contribution for the special issue of Natural Product Research on the 70th birthday of Prof. Dr Atta-ur-Rahman.

Structure modeling of a metalloendopeptidase from Corynebacterium pseudotuberculosis

Metalloendopeptidases are zinc-dependent hydrolases enzymes with many different roles in biological systems, ranging from remodeling conjunctive tissue to removing signaling sequences from nascent proteins. Here, we describe the three-dimensional structure of the metalloendopeptidase from Corynebacterium pseudotuberculosis generated by homology modeling and molecular dynamics. Analysis of key distances shows that His-132, Asp-136, His-211, Leu-212 and one molecule of water play an important role in the protein-Zn(2+) ion interaction. The model obtained may provide structural insights into this enzyme and can be useful for the design of new caseous lymphadenitis vaccines based on genetic attenuation from key point mutation.