The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

The modern approach to the development of new chemical entities against complex diseases, especially the neglected endemic diseases such as tuberculosis and malaria, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a defined target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, (iii) the development even in the initial stages of compounds with selective toxicity (the fundamental principle of chemotherapy), (iv) the evaluation of plant extracts as well as of pure substances. The current use of such technology, unfortunately, is concentrated in developed countries, especially in the big pharma. This fact contributes in a significant way to hamper the development of innovative new compounds to treat neglected diseases. The large biodiversity within the territory of Brazil puts the country in a strategic position to develop the rational and sustained exploration of new metabolites of therapeutic value. The extension of the country covers a wide range of climates, soil types, and altitudes, providing a unique set of selective pressures for the adaptation of plant life in these scenarios. Chemical diversity is also driven by these forces, in an attempt to best fit the plant communities to the particular abiotic stresses, fauna, and microbes that co-exist with them. Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest, Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of environments to be used to search for natural compounds active against tuberculosis, malaria, and chronic-degenerative diseases. The present review describes some strategies to search for natural compounds, whose choice can be based on ethnobotanical and chemotaxonomical studies, and screen for their ability to bind to immobilized drug targets and to inhibit their activities. Molecular cloning, gene knockout, protein expression and purification, N-terminal sequencing, and mass spectrometry are the methods of choice to provide homogeneous drug targets for immobilization by optimized chemical reactions. Plant extract preparations, fractionation of promising plant extracts, propagation protocols and definition of in planta studies to maximize product yield of plant species producing active compounds have to be performed to provide a continuing supply of bioactive materials. Chemical characterization of natural compounds, determination of mode of action by kinetics and other spectroscopic methods (MS, X-ray, NMR), as well as in vitro and in vivo biological assays, chemical derivatization, and structure-activity relationships have to be carried out to provide a thorough knowledge on which to base the search for natural compounds or their derivatives with biological activity.

Statistics and kinetics of single-molecule electron transfer dynamics in complex environments: A simulation model study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Structure and Growth Kinetics of 3-Glycidoxypropyltrimethoxysilane-Derived Organic/Silica Hybrids at Different Temperatures

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dynamic Scaling and Growth Kinetics of 3-Glycidoxypropyltrimethoxysilane-Derived Organic/Silica Hybrids

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Temperature Effect on the Structure and Formation Kinetics of Vinyltriethoxysilane-Derived Organic/Silica Hybrids

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Drying rates of Rubi grapes submitted to chemical pretreatments for raisin production

O objetivo deste trabalho foi selecionar o pré-tratamento químico mais apropriado para a secagem de uvas cv. Rubi para a produção de passas. Foram obtidas curvas de secagem convectiva com ar a 50ºC, em um secador de bandejas, para uvas submetidas a pré-tratamentos químicos com diferentes concentrações de carbonato de potássio e azeite de oliva, e diferentes tempos de imersão, de acordo com planejamentos fatoriais. Também foram obtidas curvas de secagem convectiva, para uvas pré-tratadas em suspensões aquosas de lecitina de soja, em várias concentrações de lecitina e diferentes tempos de imersão. O modelo de Page foi ajustado às curvas de secagem experimental, e os tempos de secagem calculados mostraram que o melhor pré-tratamento consistiu na imersão das uvas por 2 minutos, em uma emulsão de 5% de azeite de oliva e 6% de K2CO3, a 50ºC, o que resultou em tempos de secagem próximos aos do pré-tratamento com 2,5% de azeite de oliva, mas com um menor consumo dessa substância. Além disso, a imersão das uvas em uma suspensão aquosa de 2% de lecitina de soja, a 50ºC, por 5 minutos, resultou em um tempo de secagem total apenas levemente superior ao do pré-tratamento mais efetivo.

Growth kinetics of tin oxide nanocrystals in colloidal suspensions under hydrothermal conditions

Colloidal suspensions of tin oxide nanocrystals were synthesized at room temperature by the hydrolysis reaction of tin chloride (II), in an ethanolic solution. The coarsening kinetics of such nanocrystals was studied by submitting the as-prepared suspensions to hydrothermal treatments at temperatures of 100, 150 and 200 degrees C for periods between 60 and 12,000 min. Transmission electron microscopy (TEM) was used to characterize the samples (i.e. distribution of nanocrystal size, average particle radius and morphology). The results show that the usual Ostwald ripening coarsening mechanism does not fit well the experimental data, which is an indicative that this process is not significant for SnO2 nanocrystals, in the studied experimental conditions. The morphology evolution of the nanocrystals upon hydrothermal treatment indicates that growth by oriented attachment (OA) should be significant. A kinetic model that describes OA growth is successfully applied to fit the data. (c) 2006 Elsevier B.V. All rights reserved.

Effect of chemical pretreatment on the physical properties of dehydrated grapes

The effects of chemical pretreatment and air drying temperature on drying kinetics, shrinkage, density and rehydration ratio of grapes were determined at various moisture contents. It was observed that the chemical pretreatment employed - a solution of 2% CaCO3 with 0 to 3% ethyl oleate - increased considerably the drying rate. It was established that the shrinkage increased with drying temperature between 40 to 80 degrees C and decreased with increasing concentration of ethyl oleate in the chemical pretreatment solution.

A nonisothermal study of the kinetics of the nanoporosity elimination in sonogels-derived silica xerogels

A nonisothermal study of the kinetics of the nanoporosity elimination in monolithic silica xerogels, prepared from acid and ultrasound catalyzed hydrolysis of tetraethylortosilicate (TEOS), has been carried out by means of in situ linear shrinkage measurements performed with different heating rates. The study could be applied up to almost alpha similar to 0.6 of the volume fraction alpha of eliminated pores. The activation energy was found increasing from about 3.2 x 10(2) kJ/mol for alpha similar to 0.06 up to about 4.4 x 10(2) kJ/mol for alpha. similar to 0.44. The sintering process accompanying the nanopore elimination in this set of xerogels is in agreement with a viscous flux sintering process with the hydroxyl content diminishing with the volume fraction of eliminated pores. All the volume fraction of eliminated pores versus temperature (T) curves can be matched onto a unique curve with an appropriate rescaling of the T axis, independent of the heating rate. This scaling property suggests that the path of sintering seems the same, regardless of the heating rate; the difference is that the rate is faster at higher temperature.

Poly(hydroxybutyrate-co-hydroxyvalerate) microspheres loaded with atrazine herbicide: screening of conditions for preparation, physico-chemical characterization, and in vitro release studies

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Capacitance Spectroscopy: A Versatile Approach To Resolving the Redox Density of States and Kinetics in Redox-Active Self-Assembled Monolayers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Electrogravimetric Real-Time and in Situ Michaelis-Menten Enzimatic Kinetics: Progress Curve of Acetylcholinesterase Hydrolysis

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Kinetics and mechanism of the forward and reverse reactions between N,N′-dimethyl-4,4′-bipyridinium and hexacyanoferrate(II)

The kinetics of the hexacyanoferrate(III)-N,N′-dimethyl-4,4′-bipyridinium radical (MV+) reaction was studied by a laser flash photolysis technique. The radical was generated, in the presence of Fe(CN)6 3-, by quenching the excited state *Ru(bpy)3 2+ with MV2+. The second-order rate constant for the Fe(CN)6 3--MV+ reaction is (7.6 ± 0.5) × 109 M-1 s-1 at 23°C and ionic strength 0.10 M. Comparison with the rate constants calculated for the diffusion-controlled reaction (4.7 × 109 M-1 s-1) and the activation-controlled reaction (5.2 × 1012 M-1 s-1, on the basis of self-exchange rate constants of 8.0 × 105 M-1 s-1 and 1.9 × 104 M-1 s-1 for the MV2+/+ and Fe(CN)6 3-/4- couples, respectively) leads to the conclusion that the Fe(CN)6 3--MV+ reaction is diffusion controlled. The rate constant for the Fe(CN)6-MV2+ reaction, calculated from the rate constant for the Fe(CN)6 3--MV+ reaction and the appropriate equilibrium constant, is 2.4 × 10-5 M-1 s-1 at 23°C and ionic strength 0.10 M. Microscopic reversibility considerations require that the Fe(CN)6 4--MV2+ reaction be controlled by the dissociation of the successor complex Fe(CN)6 3-|MV+. The thermal and optical electron transfers in the ion pair Fe(CN)6 4-|MV2+ and in related systems are analyzed and discussed. © 1982 American Chemical Society.

Kinetics of the reaction of alkylamines with 7,7,8,8-tetracyanoquinodimethane (TCNQ) in organic solvents

The following sequence of substitution reactions was studied spectrophotometrically in organic solvents: RNH2 + TCNQ →-HCN 7-substituted TCNQ →-HCN +RNH2 7.7-disubstituted TCNQ where R = butyl, octyl, dodecyl, and hexadecyl. The production of 7-(alkylamino)-7,7,8-tricyanoquinodimethanes proceeds via the formation of the anion radical of TCNQ (TCNQ-·) whose rate of appearance was found to be a function of the chain length of R, reaching a maximum for octylamine. The formation of TCNQ-· was sensitive to the solvent polarity and electron-donor power and was associated with a small enthalpy and a highly negative entropy of activation. Above a certain [C8H17NH2] the rate of disappearance of TCNQ-· was independent of the amine concentration, and the reaction had a much higher enthalpy and entropy of activation. The occurrence of tautomerism precluded an investigation of the conversion of 7-(octylamino)-7,8,8-tricyanoquinodimethane into 7,7-bis(octylamino)-8,8-dicyanoquinodimethane. A study of the reaction of octylamine with 7-morpholino-7,8,8-tricyanoquinodimethane (which does not exist in tautomeric forms) showed that the second substitution step proceeds with the same mechanism as the first one. The only difference between the two compounds (TCNQ and its monosubstituted morpholino derivative) is one of reactivity. © 1985 American Chemical Society.