892 resultados para ANTITUMOR AGENTS


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We study a dynamic model of coordination with timing frictions and payoff heterogeneity. There is a unique equilibrium, characterized by thresholds that determine the choices of each type of agent. We characterize equilibrium for the limiting cases of vanishing timing frictions and vanishing shocks to fundamentals. A lot of conformity emerges: despite payoff heterogeneity, agents’ equilibrium thresholds partially coincide as long as there exists a set of beliefs that would make this coincidence possible – though they never fully coincide. In case of vanishing frictions, the economy behaves almost as if all agents were equal to an average type. Conformity is not inefficient. The efficient solution would have agents following others even more often and giving less importance to the fundamental

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Sulfated polysaccharides comprise a complex group of macromolecules with a range of several biological activities, including antiviral activity, anticoagulant, antiproliferative, antiherpética, antitumor, anti-inflammatory and antioxidant. These anionic polymers are widely distributed in tissues of vertebrates, invertebrates and algae. Seaweeds are the most abundant sources of sulfated polysaccharides in nature. The green algal sulfated polysaccharides are homo or heteropolysaccharides comprised of galactose, glucose, arabinose and/or glucuronic acid. They are described as anticoagulant, anti-inflammatory, antiviral, anti-angiogenic, antitumor compounds. However, there are few studies about elucidation and evaluation of biological/pharmacological effects of sulfated polysaccharides obtained from green algae, for example, there is only one paper reporting the antinociceptive activity of sulfated polysaccharides of these algae. Therefore this study aimed to obtain sulfated polysaccharides of green seaweed Codium isthmocladum and evaluates them as potential antinociceptive agents. Thus, in this study, the total extract of polysaccharides of green alga C. isthmocladum was obtained by proteolytic digestion, followed by fractionation resulting in five fractions (F0.3, F0.5, F0.7, F0.9 and F1.2) by sequential precipitation with acetone. Using the test of abdominal contractions we observed that the fraction F0.9 was the most potent antinociceptive aompound. F0.9 consists mainly of a sulfated heterogalactana. More specific tests showed that Fo.9 effect is dose and time dependent, reaching a maximum at 90 after administration (10 mg / kg of animal). F0.9 is associated with TRPV1 and TRPA1 receptors and inhibits painful sensation in animals. Furthermore, F0.9 inhibits the migration of lymphocytes induced peritonitis test. On the other hand, stimulates the release of NO and TNF-α. These results suggest that F0.9 has the potential to be used as a source of sulfated galactan antinociceptive and anti-inflammatory

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Seaweeds are organisms known to exhibit a variety of biomolecules with pharmacological properties. The coast of Rio Grande do Norte has over 100 species of seaweeds, most of them not yet explored for their pharmacological potential. Sugars and phenolic compounds are the most studied of these being assigned a range of biological properties, such as anticoagulant , antiinflammatory, antitumor and antioxidant activities. In this work, we obtained methanolic extracts from thirteen seaweeds of the coast of Rio Grande do Norte (Dictyota cervicornis; Dictiopterys delicatula; Dictyota menstruallis; D. mertensis; Sargassum filipendula; Spatoglossum schröederi; Acanthophora specifera; Botryocladia occidentalis; Caulerpa cupresoides; C. racemosa; C. prolifera; C. sertularioides e Codium isthmocladum). They were evaluated as anticoagulant and antioxidant drugs, as well as antiproliferative drugs against the tumor cell line HeLa. None of the methanolic extracts showed anticoagulant activity, but when they were evaluated as antioxidant drugs all of extracts showed antioxidant activity in all tests performed (total antioxidant capacity, sequestration of superoxide and hydroxyl radicals, ferric chelation and reductase activity), especially the algae D. mentrualis, D. cilliolata and C. prolifera, who had the greatest potential to donate electrons.In addition, the ability of iron ions chelation appears as the main antioxidant mechanism of the methanolic extracts of these seaweeds mainly for the extract of the C. racemosa seaweed, which reached almost 100% activity. In the MTT assay, all extracts showed inhibitory activity at different levels againts HeLa cells. Moreover, D. cilliolata (MEDC) and D. menstrualis (MEDM) extracts showed specific activity to this cell line, not inhibiting the viability of 3T3 normal cell line, so they were chosen for detailing the antiproliferative mechanism of action. Using flow cytometry, fluorescence microscopy and in vitro assays we demonstrated that MEDC and MEDM induced apoptosis in HeLa cells by activation of caspases 3 and 9 and yet, MEDC induces cell cycle arrest in S phase. Together, these results showed that the methanolic extracts of brown seaweed D. menstrualis and D. cilliolata may contain agents with potential use in combatting cells from human uterine adenocarcinoma. This study also points to the need for more in-depth research on phytochemical and biological context to enable the purification of biologically active products of these extracts

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

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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This study describes the synthesis, IR, (1)H, and (13)C{(1)H} NMR spectroscopic as well the thermal characterization of the new palladium(II) pyrazolyl complexes [PdCl(2)(HmPz)(2)] 1, [PdBr(2)(HmPz)(2)] 2, [PdI(2)(HmPz)(2)] 3, [Pd(SCN)(2)(HmPz)(2)] 4 {HmPz = 4-methylpyrazole}. The residues of the thermal decomposition were identified as Pd(0) by X-ray powder diffraction. From the initial decomposition temperatures, the thermal stability of the complexes can be ordered in the sequence: 1 > 2 > 4 a parts per thousand 3. The cytotoxic activities of the complexes and the ligand were investigated against two murine cancer cell lines: mammary adenocarcinoma (LM3) and lung adenocarcinoma (LP07) and compared to cisplatin under the same experimental conditions.

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

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The pyrazole ligand 3,5-dimethyl-4-iodopyrazole (HdmIPz) has been used to obtain a series of palladium(II) complexes (1-4) of the type [PdX(2)(HdmIPz)(2)] {X = Cl(-) (1); Br(-) (2); I(-) (3); SCN(-) (4)}. All compounds have been isolated, purified, and characterized by means of elemental analysis, IR spectroscopy, (1)H and (13)C{(1)H}-NMR experiments, differential thermal analysis (DTA), and thermogravimetry (TG). The TG/DTA curves showed that the compounds released ligands in the temperature range 137-605 A degrees C, yielding metallic palladium as final residue. The complexes and the ligand together with cisplatin have been tested in vitro by MTT assay for their cytotoxicity against two murine cancer cell lines: mammary adenocarcinoma (LM3) and lung adenocarcinoma (LP07).

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Currently, a wide range of research involving natural products is focused on the discovery of new drugs in many different therapeutic areas. A great number of the synthetic compounds on the market were derived from natural products, especially plants. Nemorosone is the major constituent of the floral resin of Clusia rosea Jacq., Clusiaceae, and in Cuban propolis. In vitro studies have shown cytotoxic activity in this substance against various tumor cell lines, including those resistant to various cytotoxic drugs, whereas it has low cytotoxicity to non-tumoral cells. Therefore, in order to characterize the biological activity of nemorosone, a substance with potential antitumor activity, and in view of preclinical testing of the toxicity of drug candidate compounds, the main aim of this study was to determine the mutagenic and antimutagenic activity of nemorosone by the Ames test, using the strains TA97a, TA98, TA100 and TA102 of Salmonella typhimurium. Secondly, to characterize the estrogenic activity in an experimental recombinant yeast model (Recombinant Yeast Assay) mutagenic activity was observed at in any of the concentrations in any of the test strains. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine (NPD), mitomycin C (MMC) and aflatoxin B1 (AFL). Nemorosone showed moderate antimutagenic activity (inhibition level 31%), in strain TA100 in the presence of AFL, and strong antimutagenic activity in TA102 against MMC (inhibition level 53%). Estrogenic activity was observed, with an EEq of 0.41±0.16 nM at various tested concentrations.

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The Topliss method was used to guide a synthetic path in support of drug discovery efforts toward the identification of potent antimycobacterial agents. Salicylic acid and its derivatives, p-chloro, p-methoxy, and m-chlorosalicylic acid, exemplify a series of synthetic compounds whose minimum inhibitory concentrations for a strain of Mycobacterium were determined and compared to those of the reference drug, p-aminosalicylic acid. Several physicochemical descriptors (including Hammett's sigma constant, ionization constant, dipole moment, Hansch constant, calculated partition coefficient, Sterimol-L and -B-4 and molecular volume) were considered to elucidate structure-activity relationships. Molecular electrostatic potential and molecular dipole moment maps were also calculated using the AM1 semi-empirical method. Among the new derivatives, m-chlorosalicylic acid showed the lowest minimum inhibitory concentration. The overall results suggest that both physicochemical properties and electronic features may influence the biological activity of this series of antimycobacterial agents and thus should be considered in designing new p-aminosalicylic acid analogs.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)