Descripción: This paper reports a synthesis of novel diheteroarylethenes functionalized for coupling to biomolecules starting from indole derivatives. The strategy is based on the derivatization at the N-atom in the indole substructure. TBDMS protection proved to be superior over BOC protection schemes, leading to higher yields in the overall synthesis. The suitability of the new derivatives as acceptors for pcFRET was calculated for selected donors.

Descripción: The complete set of concomitants is given of the metric, a scalar function, and their derivatives in six dimensions without imposing conditions on the order of the derivatives and their properties are studied under conformal transformations. These results are useful in several physical problems, like finding φ2ren and Τμν ren in any geometry. © 1992 American Institute of Physics.

Descripción: The resolution of molecular electric dipole polarizabilities into atomic contributions was studied in the context of methyl and ethyl derivatives, CH3-X and CH3-CH2-X. The reliability of the partitioning schemes allowing for adhoc quantum chemical tools was also tested. Results depicted a good degree of the transferability from molecule to molecule as shown by the evaluation of gross atomic isotropic contributions for carbon, hydrogen, and heteroatoms.

Descripción: The synthesis of some isoxazolic compounds from carbohydrate derivatives is described. These products are obtained by 1,3-dipolar cycloaddition reaction and their functionalization leads to derivatives with potential biological activities.

Descripción: The aim of this work was to test in vitro and in vivo the efficacy of the derivatives of 5-aminolevulinic acid (ALA): hexyl-ALA (He-ALA), undecanoyl-ALA and R,S-2-(hydroximethyl)tetrahydropyranyl-ALA (THP-ALA) as pro-photosensitising agents. The compounds were assayed in a cell line derived from a murine mammary tumour, in tumour explants and after injection of the cells into mice. In vitro, undecanoyl-ALA and THP-ALA did not improve ALA efficacy in terms of porphyrin synthesis. On the other hand, half of the amount of ALA is required to obtain the same plateau amount of photosensitiser from He-ALA. However, this plateau value cannot be surpassed in spite of the four-times higher accumulation of ALA/He-ALA from the ALA derivative. This shows that He-ALA conversion to porphyrins but not He-ALA entry to the cells is limiting. Employing ionic exchange chromatography, we found that 80% of total uptake was He-ALA whereas only 20% was ALA. This suggests that the esterases, probably themselves regulated by the heme pathway, are limiting the conversion of ALA derivatives into porphyrins. A similar situation occurs with THP-ALA. Tumour explant porphyrin results correlate well with cell line data. However, i.p. injection of ALA derivatives to mice resulted in a lower porphyrin concentration in the tumour when compared to the administration of equimolar amounts of ALA, indicating that there should be retention of ALA derivatives either within the blood vessels in the initial phase of distribution and/or within the capillaries of the tumour. © 2004 Cancer Research UK.

Descripción: We introduce an effective one-uid description of the interacting dark sector in a spatially at Friedmann-Robertson-Walker space-time and investigate the stability of the power-law solutions. We find the "source equation" for the total energy density and determine the energy density of each dark component. We study linear and nonlinear interactions which depend on the dark matter and dark energy densities, their first derivatives, the total energy density with its derivatives up to second order and the scale factor. We solve the evolution equations of the dark components for both interactions, examine exhaustively several examples and show cases where the problem of the coincidence is alleviated. We show that a generic nonlinear interaction gives rise to the "relaxed Chaplygin gas model" whose effective equation of state includes the variable modified Chaplygin gas model while some others nonlinear interactions yield de Sitter and power-law scenarios. © 2012 American Institute of Physics.

Descripción: A series of acyl esters of 3,17-β-estradiol has been prepared by an enzymatic methodology. Eleven 17-monoacyl products (five novel compounds) were obtained in a highly regioselective way by acylation of 3,17-β-estradiol or by alcoholysis of the corresponding diacyl derivatives. The influence of various reaction parameters such as molar ratio, enzyme:substrate ratio and temperature was evaluated. Among the tested lipases, Candida rugosa lipase appeared to be the most appropriate in monoacylation and lipase from Candida antarctica in alcoholysis. The advantages presented by this methodology such as mild reaction conditions, economy and low environmental impact, make the biocatalysis a convenient way to prepare monoacyl derivatives of 3,17-β-estradiol containing the aromatic 3-hydroxyl group free. Some of these compounds are recongnized as useful products in the pharmaceutical industry. ©ARKAT.

Descripción: The Taylor microscale, a measure of mean square spatial derivatives, is evaluated for interplanetary magnetic field fluctuations from single- and multiple-point data using Cluster and ACE spacecraft data. The Taylor scale is compared to the measured inner scale, which for hydrodynamics would correspond to the Kolmogorov scale. The results are not consistent with dissipation of the hydrodynamic type, and indicate that solar wind dissipation involves kinetic plasma physics at both proton and electron scales. © 2008. The American Astronomical Society. All rights reserved.

Descripción: The use of more lipophilic derivatives of 5-aminolevulinic acid (ALA) is expected to have better diffusing properties, and after conversion into the parent ALA, to reach a higher protoporphyrin IX (PPIX) formation rate, thus improving the efficacy of topical photodynamic therapy (PDT). Here we have analysed the behaviour of 3 ALA derivatives (ALA methyl-ester, hexyl ester and a 2-sided derivative) regarding PPIX formation, efficiency in photosensitizing cells and mechanism of cellular death. The maximum amount of porphyrins synthesized from 0.6 mM ALA was 47 ± 8 ng/105 cells. The same amount was formed by a concentration 60-fold lower of hexyl-ALA and 2-fold higher of methyl-ALA. The 2-sided derivative failed to produce PPIX accumulation. Applying a 0.6 J cm-2 light dose, cell viability decreased to 50%. With the 1.5 J cm-2 light dose, less than 20% of the cells survive, and higher light doses produced nearly total cell killing. Comparing the PPIX production and the induced phototoxicity, the more the amount of porphyrins, the greater the cellular killing, and PPIX formed from either ALA or ALA-esters equally sensitize the cells to photoinactivation. ALA-PDT treated cells exhibited features of apoptosis, independently on the pro-photosensitizer employed. ALA-PDT can be improved with the use of ALA derivatives, reducing the amount of ALA necessary to induce efficient photosensitization. © 2001 Cancer Research Campaign.

Descripción: 4-O-Substituted D-glucuronic acid derivatives were synthesized from D-glucose in order to study the regioselectivity of sulfation.

Descripción: β-Lapachone, an o-naphthoquinone, induces a novel caspase- and p53-independent apoptotic pathway dependent on NAD (P) H:quinone oxidoreductase 1 (NQO1). NQO1 reduces β-lapachone to an unstable hydroquinone that rapidly undergoes a two-step oxidation back to the parent compound, perpetuating a futile redox cycle. A deficiency or inhibition of NQO1 rendered cells resistant to beta;-lapachone. Thus, β-lapachone has great potential for the treatment of specific cancers with elevated NQO1 levels (e.g., breast, non - small cell lung, pancreatic, colon, and prostate cancers). We report the development of mono(arylimino) derivatives of β-lapachone as potential prodrugs. These derivatives are relatively nontoxic and not substrates for NQO1 when initially diluted in water. In solution, however, they undergo hydrolytic conversion to β-lapachone at rates dependent on the electron-withdrawing strength of their substituent groups and pH of the diluent. NQO1 enzyme assays, UV-visible spectrophotometry, high-performance liquid chromatography-electrospray ionization-mass spectrometry, and nuclear magnetic resonance analyses confirmed and monitored conversion of each derivative to β-lapachone. Once converted, β-lapachone derivatives caused NQO1-dependent, μ-calpain-mediated cell death in human cancer cells identical to that caused by β-lapachone. Interestingly, coadministration of N-acetyt-L-cysteine prevented derivative-induced cytotoxicity but did not affect β-lapachone lethality. Nuclear magnetic resonance analyses indicated that prevention of β-lapachone derivative cytotoxicity was the result of direct modification of these derivatives by N-acetyl-L-cysteine, preventing their conversion to β-lapachone. The use of β-lapachone mono(arylimino) prodrug derivatives, or more specifically a derivative converted in a tumor-specific manner (i.e., in the acidic local environment of the tumor tissue), should reduce normal tissue toxicity while eliciting tumor-selective cell killing by NQO1 bioactivation. © 2005 American Association for Cancer Research.

Descripción: Chagas' disease, caused by Trypanosoma cruzi, affects about 18 million people in Latin America, and no effective treatment is available to date. To acquire sialic acid from the host glycoconjugates, T. cruzi expresses an unusual surface sialidase with trans-sialidase activity (TcTS) that transfers the sugar to parasite mucins. Surface sialic acid was shown to have relevant functions in protection of the parasite against the lysis by complement and in mammalian host cell invasion. The recently determined 3D structure of TcTS allowed a detailed analysis of its catalytic site and showed the presence of a lactose-binding site where the β-linked galactose accepting the sialic acid is placed. In this article, the acceptor substrate specificity of lactose derivatives was studied by high pH anion-exchange chromatography with pulse amperometric detection. The lactose open chain derivatives lactitol and lactobionic acid, as well as other derivatives, were found to be good acceptors of sialic acid. Lactitol, which was the best of the ones tested, effectively inhibited the transfer of sialic acid to N-acetyllactosamine. Furthermore, lactitol inhibited parasite mucins re-sialylation when incubated with live trypanosomes and TcTS. Lactitol also diminished the T. cruzi infection in cultured Vero cells by 20-27%. These results indicate that compounds directed to the lactose binding site might be good inhibitors of TcTS. © Oxford University Press 2004; all rights reserved.

Descripción: A method is developed to solve Laplace's equation with Dirichlet's or Neumann's conditions in plane, single-connected regions bounded by arbitrary single curves. It is based on the existence of a conformal transformation that reduces the original problem to another whose solution is known. The main advantage of the method is that it does not require the knowledge of the transformation itself, so it is applicable even when no transformation is available. The solution and its higher-order derivatives are expressed in terms of explicit quadratures easy to evaluate numerically or even analytically. © 1990 American Institute of Physics.

Descripción: The deposition of fibrillar structures (amyloids) is characteristic of pathological conditions including Alzheimer's and Parkinson's diseases. The detection of protein deposits and the evaluation of their kinetics of aggregation are generally based on fluorescent probes such as thioflavin T and Congo red. In a search for improved fluorescence tools for studying amyloid formation, we explored the ability of N-arylaminonaphthalene sulfonate (NAS) derivatives to act as noncovalent probes of α-synuclein (AS) fibrillation, a process linked to Parkinson's disease and other neurodegenerative disorders. The compounds bound to fibrillar AS with micromolar Kds, and exhibited fluorescence enhancement, hyperchromism, and high anisotropy. We conclude that the probes experience a hydrophobic environment and/or restricted motion in a polar region. Time- and spectrally resolved emission intensity and anisotropy provided further information regarding structural features of the protein and the dynamics of solvent relaxation. The steady-state and time-resolved parameters changed during the course of aggregation. Compared with thioflavin T, NAS derivatives constitute more sensitive and versatile probes for AS aggregation, and in the case of bis-NAS detect oligomeric as well as fibrillar species. They can function in convenient, continuous assays, thereby providing useful tools for studying the mechanisms of amyloid formation and for high-throughput screening of factors inhibiting and/or reversing protein aggregation in neurodegenerative diseases. © 2008 by the Biophysical Society.

Descripción: The title compound, N-[2-(5-methoxy-1-nitroso-1H-indol-3-yl)ethyl]acetamide, C13H15N3O3, an N-nitroso derivative of melatonin, crystallizes in the monoclinic C2/c space group. The molecules are arranged in such a way that the aromatic rings are in a planar conformation, with the alkylamide side chains in a different plane, at a dihedral angle of 108.60 (6)°. The alkylamide chains are interconnected by hydrogen bonds, constituting an infinite array.

Descripción: Yerba maté extracts have in vitro antioxidant capacity attributed to the presence of polyphenolic compounds, mainly chlorogenic acids and dicaffeoylquinic acid derivatives. DPPH is one of the most used assays to measure the antioxidant capacity of pure compounds and plant extracts. It is difficult to compare the results between studies because this assay is applied in too many different conditions by the different research groups. Thus, in order to assess the antioxidant capacity of yerba maté extracts, the following procedure is proposed: 100 μL of an aqueous dilution of the extracts is mixed in duplicate with 3.0 mL of a DPPH 'work solution in absolute methanol (100 μM.L-1), with an incubation time of 120 minutes in darkness at 37 ± 1 °C, and then absorbance is read at 517 nm against absolute methanol. The results should be expressed as ascorbic acid equivalents or Trolox equivalents in mass percentage (g% dm, dry matter) in order to facilitate comparisons. The AOC of the ethanolic extracts ranged between 12.8 and 23.1 g TE % dm and from 9.1 to 16.4 g AAE % dm. The AOC determined by the DPPH assay proposed in the present study can be related to the total polyphenolic content determined by the Folin-Ciocalteu assay.

Descripción: In this article we evaluate the Fourier transforms of retarded Lorentz-invariant functions (and distributions) as limits of Laplace transforms. Our method works generally for any retarded Lorentz-invariant functions φ(t) (t ε{lunate} Rn) which is, besides, a continuous function of slow growth. We give, among others, the Fourier transform of GR(t, α, m2, n) and GA(t, α, m2, n), which, in the particular case α = 1, are the characteristic functions of the volume bounded by the forward and the backward sheets of the hyperboloid u = m2 and by putting α = -k are the derivatives of k-order of the retarded and the advanced-delta on the hyperboloid u = m2. We also obtain the Fourier transform of the function W(t, α, m2, n) introduced by M. Riesz (Comm. Sem. Mat. Univ. Lund4 (1939)). We finish by evaluating the Fourier transforms of the distributional functions GR(t, α, m2, n), GA(t, α, m2, n) and W(t, α, m2, n) in their singular points. © 1981.

Descripción: In this work we analyze the existence and regularity of the solution of a nonhomogeneous Neumann problem for the Poisson equation in a plane domain Ω with an external cusp. In order to prove that there exists a unique solution in H1 (Ω) using the Lax-Milgram theorem we need to apply a trace theorem. Since Ω is not a Lipschitz domain, the standard trace theorem for H1 (Ω) does not apply, in fact the restriction of H1 (Ω) functions is not necessarily in L2 (∂Ω). So, we introduce a trace theorem by using weighted Sobolev norms in Ω. Under appropriate assumptions we prove that the solution of our problem is in H2 (Ω) and we obtain an a priori estimate for the second derivatives of the solution. © 2005 Elsevier Inc. All rights reserved.

Descripción: The topological analysis from Bjorkman (1995) for the standard model that describes the winds from hot stars by Castor et al. (1975) has been extended to include the effect of stellar rotation and changes in the ionization of the wind. The differential equation for the momentum of the wind is non-linear and transcendental for the velocity gradient. Due to this non-linearity the number of solutions that this equation possess is not known. After a change of variables and the introduction of a new physically meaningless independent variable, we manage to replace the non-linear momentum differential equation by a system of differential equations where all the derivatives are explicitely given. We then use this system of equations to study the topology of the rotating-CAK model. For the particular case when the wind is frozen in ionization (δ = 0) only one physical solution is found, the standard CAK solution, with a X-type singular point. For the more general case (δ ≠ 0), besides the standard CAK singular point, we find a second singular point which is focal-type (or attractor). We find also, that the wind does not adopt the maximal mass-loss rate but almost the minimal.