A new bianthron glycoside as inhibitor of Trypanosoma cruzi glyceraldehyde 3-phosphate dehydrogenase activity

A phytochemical investigation of the ethanolic extract of stalks of Senna martiana Benth. (Leguminoseae), native specie of northeast Brazil, resulted in the isolation and spectroscopic characterization of a new bianthrone glycoside, martianine 1 (10,10'-il-chrysophanol-10-oxi10,10'-bi-glucosyl). Its identification was established by HRMS, IR and 2D NMR experiments. The evaluation of martianine trypanocidal activity was carried out against gliceraldehyde 3-phosphate dehydrogenase enzyme from Trypanosoma cruzi. Its inhibitory constant (Ki) is in the low micromolar concentration and it was determined by isothermal titration calorimetry to be 27.3 ± 2.47 µmol L-1. The non-competitive mechanism is asserted to be putative of the mode of action martianine displays against T. cruzi GAPDH. Results show that martianine has a great potential to become new lead molecule by inhibiting this key enzyme and for the development of new drugs against Chagas disease.

Synthesis, screening for antiacetylcholinesterase activity and binding mode prediction of a new series of [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters

A series of nine new [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters (phosphate-carbamate compounds) was obtained through the reaction of (4,4,4-trifluoro-3-hydroxybut-1-yl)-carbamic acid ethyl esters with phosphorus oxychloride followed by the addition of alcohols. The products were characterized by ¹H, 13C, 31P, and 19F NMR spectroscopy, GC-MS, and elemental analysis. All the synthesized compounds were screened for acetylcholinesterase (AChE) inhibitory activity using the Ellman method. All compounds containing phosphate and carbamate pharmacophores in their structures showed enzyme inhibition, being the compound bearing the diethoxy phosphate group (2b) the most active compound. Molecular modeling studies were performed to investigate the detailed interactions between AChE active site and small-molecule inhibitor candidates, providing valuable structural insights into AChE inhibition.

Screening of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase enzyme inhibitors

The inhibitory activity of crude extracts of Meliaceae and Rutaceae plants on glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) enzyme from Trypanosoma cruzi was evaluated at 100 μg/mL. Forty-six extracts were tested and fifteen of them showed significant inhibitory activity (IA % > 50). The majority of the assayed extracts of Meliaceae plants (Cedrela fissilis, Cipadessa fruticosa and Trichilia ramalhoi) showed high ability to inhibit the enzymatic activity. The fractionation of the hexane extract from branches of C. fruticosa led to the isolation of three flavonoids: flavone, 7-methoxyflavone and 3',4',5',5,7-pentamethoxyflavone. The two last compounds showed high ability to inhibit the gGAPDH activity. Therefore, the assayed Meliaceae species could be considered as a promising source of lead compounds against Chagas' disease.

Unusual 1,6-diphenyl-1,3,5-hexatriene (DPH) spectrophotometric behavior in water/ethanol and water/DMSO mixtures

The absorption spectra of DPH at fixed concentration do not change with water content in organic solvents. It exhibits monomer bands, such as those obtained in ethanol. The absorption did not change for solutions up to 54 and 46% of water in ethanol and DMSO, respectively, for [DPH] = 5.0 × 10-6 mol L-1 at 30 °C. However, at the same experimental conditions, a gradual sharp decay of the DPH fluorescence is observed. It is proposed that water molecules below these water concentration limits act as quenchers of the excited states of DPH. Stern-Volmer quenching constants by intensities measurements are 7.4 × 10-2 (water/ethanol) and 2.6 × 10-2 L mol-1 (water/DMSO). DPH lifetime measurements in the absence and presence of water resulted in 7.1 × 10-2 L mol-1 in water/ethanol, which pointed out that the process is a dynamic quenching by water molecules. For experiments using DPH as probe, this process can affect data, leading to misunderstanding interpretation.

Metabólitos secundários das esponjas Aplysina fistularis e Dysidea sp. e atividade antituberculose da 11-cetofistularina-3

The present investigation reports the isolation of aeroplysinin-2, 2-(3,5-dibromo-4-methoxyphenyl)-N,N,N-trimethyletanamonium, 7,9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,6,8-trien-3-carboxylic acid and its methyl ester, 11-oxoaerothionin, aerothionin, 11-keto-12-hydroxyaerothionin, 11-ketofistularin-3 and fistularin-3 from Aplysina fistularis, as well as of furodysinin lactone and 9α,11α-epoxicholest-7-en-3β,5α,6α,10-tetrol-6-acetate from Dysidea sp. Although the extracts of both sponges displayed antituberculosis activity, only 11-ketofistularin-3 isolated from A. fistularis displayed antimycobacterial activity against Mycobacterium tuberculosis H34Rv, with MIC at 16 μg/mL and SI of 40, a result that reinforce that fistularin-3 derivatives are interesting leads for the development of antituberculosis drugs.

Characterization studies of 1-(4-cyano-2-oxo-1,2-dihydro-1-pyridyl)-3-(4-cyano-1,2-dihydro-1-pyridyl)propane formed from the reaction of hydroxide Ion with 1,3-Bis-(4-cyano pyridinium)propane

The aqueous alkaline reaction of 1,3-bis(4-cyanopyridinium)propane dibromide, a reactant constituted of two pyridinium rings linked by a three-methylene bridge, generates a novel compound,1 -(4-cyano-2-oxo-1,2-dihydro-1-pyridyl)-3-(4-cyano-1,2-dihydro-1-pyridyl)propane. The reaction pathway is attributed to the proximity of the OH- ion inserted between two pyridinium moieties, which occurs only in bis(pyridinium) derivatives connected by short methylene spacers, where charge-conformational effects are important.

Gas-phase solvolysis type reactions of SiCl3+ cations

Gas-phase SiCl3+ ions undergo sequential solvolysis type reactions with water, methanol, ammonia, methylamine and propylene. Studies carried out in a Fourier Transform mass spectrometer reveal that these reactions are facile at 10-8 Torr and give rise to substituted chlorosilyl cations. Ab initio and DFT calculations reveal that these reactions proceed by addition of the silyl cation to the oxygen or nitrogen lone pair followed by a 1,3-H migration in the transition state. These transition states are calculated to lie below the energy of the reactants. By comparison, hydrolysis of gaseous CCl3+ is calculated to involve a substantial positive energy barrier.

Electrocatalytic oxidation of methanol by the [Ru3O(OAc)6(py)2(CH3OH)]3+cluster: improving the metal-ligand electron transfer by accessing the higher oxidation states of a multicentered system

The [Ru3O(Ac)6(py)2(CH3OH)]+ cluster provides an effective electrocatalytic species for the oxidation of methanol under mild conditions. This complex exhibits characteristic electrochemical waves at -1.02, 0.15 and 1.18 V, associated with the Ru3III,II,II/Ru3III,III,II/Ru 3III,III,III /Ru3IV,III,III successive redox couples, respectively. Above 1.7 V, formation of two RuIV centers enhances the 2-electron oxidation of the methanol ligand yielding formaldehyde, in agreement with the theoretical evolution of the HOMO levels as a function of the oxidation states. This work illustrates an important strategy to improve the efficiency of the oxidation catalysis, by using a multicentered redox catalyst and accessing its multiple higher oxidation states.

Solid-phase microextraction for determination of 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone in water

Solid-phase microextraction, using on-line bis(trimethylsilyl)trifluoroacetamide derivatisation, gas chromatography, and mass spectrometry, was evaluated in the quantification of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in water samples. Fibres encompassing a wide range of polarities were used with headspace and direct immersion sampling. For the immersion procedure, various parameters affecting MX extraction, including pH, salinity, temperature, and extraction time were evaluated. The optimised method (polyacrylate fibre; 20% Na2SO4; pH 2.0; 60 min; 20 °C) was applied for reservoir chlorinated water samples-either natural or spiked with MX (50 ng L-1 and 100 ng L-1). The recovery of MX ranged from 44 to 72%. Quantification of MX in water samples was done using external standard and the selected ion monitoring mode. Correlation coefficient (0.98%), relative standard deviation (5%), limit of detection (30 ng L-1) and limit of quantification (50 ng L-1) were obtained from calibration curve.

Phlebotomines (Diptera, Psychodidae) in the Speleological Province of the Ribeira Valley: 3. Serra district - area of hostels for tourists who visit the Parque Estadual do Alto Ribeira (PETAR), state of São Paulo, Brazil

Phlebotomines (Diptera, Psychodidae) in the Speleological Province of the Ribeira Valley: 3. Area of hostels for tourists who visit the Parque Estadual do Alto Ribeira (PETAR), state of São Paulo, Brazil. The study characterizes some ecological aspects of the phlebotomine fauna in an endemic area of cutaneous leishmaniasis (CL) situated in the Serra district, Iporanga municipality where the hostels for tourists visiting the PETAR are located. Captures were undertaken on a smallholding and a small farm situated near the hostels, monthly between January/2001 and December/2003 with automatic light traps (ALT) in pigsty, hen-house and veranda of a domicile at the two sites, and in peridomicile of the small farm also with black/white Shannon traps. With the ALT a total of 87,224 phlebotomines representing 19 species and also two hybrids of Nyssomyia intermedia (Lutz & Neiva) and Nyssomyia neivai (Pinto) and two anomalous specimens were captured. The standardized index species abundance was for Ny. intermedia = 1.0 and Ny. neivai = 0.935. The highest frequencies of the smallholding occurred in the pigsty, the Williams' mean/capture for Ny. intermedia being 63.7 specimens and for Ny. neivai 29.2, and on the small farm, in the hen-house, Ny. intermedia 402.6 and Ny. neivai 116.2. A total of 863 phlebotomines (Ny. intermedia: 75.4%; Ny. neivai: 24.3%) were captured with black/white Shannon traps; females of both species being predominant in the white trap. The high frequencies of Ny. intermedia and Ny. neivai, both implicated in CL transmission, indicate the areas presenting risk of the disease.

Effect of CO2 and 1-octen-3-ol attractants for estimating species richness and the abundance of diurnal mosquitoes in the southeastern Atlantic forest, Brazil

Studies have shown that both carbon dioxide (CO2) and octenol (1-octen-3-ol) are effective attractants for mosquitoes. The objective of the present study was to evaluate the attractiveness of 1-octen-3-ol and CO2 for diurnal mosquitoes in the southeastern Atlantic forest. A Latin square experimental design was employed with four treatments: CDC-light trap (CDC-LT), CDC-LT and 1-octen-3-ol, CDC-LT and CO2 and CDC-LT with 1-octen-3-ol and CO2. Results demonstrated that both CDC-CO2 and CDC-CO2-1-octen-3-ol captured a greater number of mosquito species and specimens compared to CDC-1-octen-3-ol; CDC-LT was used as the control. Interestingly, Anopheles (Kerteszia) sp. was generally attracted to 1-octen-3-ol, whereas Aedes serratus was the most abundant species in all Latin square collections. This species was recently shown to be competent to transmit the yellow fever virus and may therefore play a role as a disease vector in rural areas of Brazil.

Molecular detection of Hepatozoon canis and Babesia canis vogeli in domestic dogs from Cuiabá, Brazil

The objective of this study was to report for the first time infection by Hepatozoon spp. and Babesia spp. in 10 dogs from the city of Cuiabá, State of Mato Grosso, central-western Brazil. A pair of primers that amplifies a 574 bp fragment of the 18S rRNA of Hepatozoon spp., and a pair of primers that amplifies a 551 bp fragment of the gene 18S rRNA for Babesia spp. were used. Six dogs were positive for Babesia spp., and 9 were positive for Hepatozoon spp. Co-infection of Babesia spp. and Hepatozoon spp. was seen in 5 dogs. Sequenced samples revealed 100% identity with B. canis vogeli, and H. canis. This is the first molecular detection of H. canis in domestic dogs from Cuiabá. Additionally, it is described for the first time the presence of B. canis vogeli circulating among dogs in Cuiabá.

Effects of different levels of protein intake and physical training on growth and nutritional status of young rats

This study aimed to investigate the effects of physical training, and different levels of protein intake in the diet, on the growth and nutritional status of growing rats. Newly-weaned Wistar rats (n=48) were distributed into six experimental groups: three of them were subjected to physical swim training (1 h per day. 5 d per week, for 4 wk, after 2 wk of familiarization) and the other three were considered as controls (non-trained). Each pair of groups, trained and non-trained, received diets with a different level of protein in their composition: 14%. 21% or 28%. The animals were euthanized at the end of the training period and the following analyses were performed: proteoglycan synthesis as a biomarker of bone and cartilage growth, IGF-I (insulin-like growth factor-I) assay as a biomarker of growth and nutritional status. total RNA and protein concentration and protein synthesis measured in vivo using a large-dose phenylalanine method. As a main finding, increased dietary protein, combined with physical training, was able to improve neither tissue protein synthesis nor muscle growth. In addition, cartilage and bone growth seem to be deteriorated by the lower and the higher levels of protein intake. Our data allow us to conclude that protein enhancement in the diet, combined with physical exercise, does not stimulate tissue protein synthesis or muscle mass growth. Furthermore, physical training, combined with low protein intake, was not favorable to bone development in growing animals

Effect of n-3 polyunsaturated fatty acids on oxidative stress in rats supplemented with different doses of fish oil

The diet and plasma lipid patterns associated with lipid oxidation susceptibility in rats fed different doses of polyunsaturated fatty acids (n-3 PUFA) from fish oil were evaluated. Wistar rats were assigned into three groups and received diets containing 8% soybean oil (SOY), 4% soybean oil + 4% fish oil (SOY-FISH) and 8% fish oil (FISH) for 21 days. Linoleic, oleic and ?-linolenic acids in SOY diets were substituted by myristic, palmitic, palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in SOY-FISH and FISH diets reducing the n-6/n-3 ratio and increasing the peroxidability index (PI). Increased dietary EPA and DHA were observed in SOY-FISH and FISH plasma at the expense of linoleic and arachidonic acid levels. Saturated fatty acids, which were significantly different between the three diets (P < 0.01), were found at the same concentration in the plasma (P = 0.23). No changes were observed in oxidative stress as measured by the concentration of thiobarbituric acid reactive substances (TBARS) expressed in brain homogenates. However, TBARS concentration in the plasma of the SOY-FISH group was higher than the other two groups (P = 0.02). The major differences between these three groups were the n-3 PUFA content (0.4, 1.8 and 3.2 g/100 g diet) and the saturates/polyunsaturates ratio (0.3, 0.5 and 0.8) for SOY, SOY-FISH, and FISH groups, respectively. Thus, n-3 PUFA intake from fish oil only when followed by a decrease in saturated/polyunsaturated fatty acids ratio increased oxidative susceptibility in rats measured by plasma TBARS concentration