Planejamento, síntese e avaliação farmacológica de compostos híbridos potencialmente ativos para o tratamento da anemia falciforme

Sickle cell disease (SCD) is a hereditary hemolytic anemia caused by the inheritance of one S hemoglobin gene from each ancestor. Patients with SCD present increased circulating levels of cytokines, including TNF-alpha (TNF-α). Hydroxyurea (HU) is the available therapeutically strategy for treatment; it acts as a source of nitric oxide and benefits patients by increasing the levels of fetal hemoglobin (HbF). Thus, within one research line that aims at finding new drugs, a series of compounds with TNF-α inhibition and nitric oxide donation properties have been synthesized in order to explore possible synergism of actions beneficial in the treatment of the disease. Six compounds were synthesized: five derivatives of organic nitrates and one of sulfonamide. The compounds, (1,3-dioxo-1,3-dihydro-2Hisoindol-2-yl) methyl nitrate (compound I); (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) ethyl nitrate (compound II); 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (compound III);4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxybenzenesulfonamide (compound IV); 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (compound V) and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) phenyl]ethyl nitrate (compound VI), were synthesized using linear synthetic methodology, with excellent overall yields. All compounds showed anti-inflammatory and analgesic effects with a reduction in 43%-65% of ear edema in mice and a reduction of 25%-42% of writhing induced by acetic acid. All compounds showed comparable reductions in the leukocyte infiltration capacity and ability to generate nitric oxide. The aryl compounds (III, IV and V) presented less mutagenic activity compared to compounds I, II and VI according to the salmonella mutagenicity assay (Ames test). Compounds IV and VI showed activity in K562 culture cells, with increases in gamma globin gene expression to levels higher than with hydroxyurea suggesting a potential to increase fetal hemoglobin. This data set characterizes new potentially useful drug candidates for the treatment of symptoms of sickle cell anemia.

Simple method for culture of peripheral blood lymphocytes of Testudinidae.

We developed and optimized a simple, efficient and inexpensive method for in vitro culture of peripheral blood lymphocytes from the Brazilian tortoise Chelonoidis carbonaria (Testudinidae), testing various parameters, including culture medium, mitogen concentration, mitotic index, culture volume, incubation time, and mitotic arrest. Peripheral blood samples were obtained from the costal vein of four couples. The conditions that gave a good mitotic index were lymphocytes cultured at 37°C in minimum essential medium (7.5 mL), with phytohemagglutinin as a mitogen (0.375 mL), plus streptomycin/penicillin (0.1 mL), and an incubation period of 72 h. Mitotic arrest was induced by 2-h exposure to colchicine (0.1 mL), 70 h after establishing the culture. After mitotic arrest, the cells were hypotonized with 0.075 M KCl for 2 h and fixed with methanol/acetic acid (3:1). The non-banded mitotic chromosomes were visualized by Giemsa staining. The diploid chromosome number of C. carbonaria was found to be 52 in females and males, and sex chromosomes were not observed. We were able to culture peripheral blood lymphocytes of a Brazilian tortoise in vitro, for the preparation of mitotic chromosomes.

Advances in drug design based on the amino acid approach: Taurine analogues for the treatment of CNS diseases

Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid) this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer's, Parkinson's, epilepsy and in the damage of retinal neurons. This review describes the CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.&; 2012 by the authors; licensee MDPI, Basel, Switzerland.

On the application of nanostructured electrodes prepared by Ti/TiO2/WO3 template : A case study of removing toxicity of indigo using visible irradiation

New assays with HepG2 cells indicate that Indigo Carmine (IC), a dye that is widely used as additive in many food and pharmaceutical industries exhibited cytotoxic effects. This work describes the development of a bicomponent nanostructured Ti/TiO2/WO3 electrode prepared by template method and investigates its efficiency in a photoelectrocatalytic method by using visible light irradiation and applied potential of 1V. After 2h of treatment there are reduction of 97% discoloration, 62% of mineralization and formation of three byproducts assigned as: 2-amine-5-sulfo-benzoic acid, 2,3-dioxo-14-indole-5-sulfonic acid, and 2-amino-α-oxo-5-sulfo-benzeneacetic acid were identified by HPLC-MS/MS. But, cytotoxicity was completely removed after 120min of treatment. © 2013 Elsevier Ltd.

Antioxidant and cytotoxic effects of crude extract, fractions and 4-nerolidylcathecol from aerial parts of pothomorphe umbellata L. (Piperaceae)

The crude ethanolic extract from aerial parts of Pothomorphe umbellata L. (Piperaceae) and fractions obtained by partitions sequentially among water-methanol, methylene chloride, and ethyl acetate, as well as the major constituent, 4-nerolidylcatechol, were, respectively, evaluated and evidenced for antioxidant and cytotoxic effects through fluorometric microplate and microculture tetrazolium assays in HL-60 cells. The crude ethanolic extract demonstrated the preeminent antioxidant activity (IC50 = 1.2 μg/mL) against exogenous cytoplasmic reactive oxygen species, followed by the water-methanolic (IC50 = 4.5 μg/mL), methylene chloride (IC 50 = 5.9 g/mL), ethyl acetate (IC50 = 8.0 g/mL), 4-nerolidylcatechol (IC50 = 8.6 g/mL), and the sterol fractions (IC50 > 12.5 μg/mL). Vitamin C, the positive control used in this assay, presented IC50 value equivalent to 1.7 μg/mL. 4-Nerolidylcatechol (IC50 = 0.4 μg/mL) and methylene chloride fraction (IC50 = 2.3 μg/mL) presented considerable cytotoxicity probably because of the presence of an o-quinone, an auto-oxidation by product of the catechol. Polar compounds, present in the ethanol extract, appear to increase the solubility and stability of the major active constituent, acting synergistically with 4-nerolidylcatechol, improving its pharmacokinetic parameters and increasing significantly its antioxidant activity which, in turn, suggests that the aqueous-ethanolic extract, used in folklore medicine, is safe and effective. © 2013 Andrey P. Lopes et al.

Aspectos fisiológicos e bioquímicos de cultivares de soja submetidos a déficit hídrico induzido por peg 6000

In soybean culture water deficit is one of the most limiting factors to the maximum yield obtained. Genotypes identification with drought tolerance capacity is fundamental to solve this problem. The objective in this paper was analyze the physiological quality and physiological and biochemical responses of soybeans cultivars (MG/BR 46 Conquista, UFUS Carajás, UFUS Impacta, UFUS Riqueza and UFUS Xavante) submitted to water stress with PEG 6000 solutions in different levels of osmotic potentials (0; -0,1; -0,2; -0,3 and -0,4 MPa). Physiological quality of cultivars were evaluated by seedling length test and fresh and dry biomass. The biochemical responses were evaluated by detection of indol-acetic acid (IAA), by saccharose content and seedling water transportation. UFUS Riqueza presented the best performance in physiological quality tests, saccharose content, absorption and water absorption velocity in seedling. UFUS Xavante showed the highest IAA's concentration and the greater weight of seedling in water transportation test.

Gastroprotective mechanisms of the chloroform and ethyl acetate phases of Praxelis clematidea (Griseb.) R.M.King & H.Robinson (Asteraceae)

Flavonoid-rich Praxelis clematidea (Griseb.) R.M.King & H.Robinson (Asteraceae) is a native plant of South America. This study evaluates the gastroprotective activity and possible mechanisms for both the chloroform (CHCl3P) and ethyl acetate phases (AcOEtP) obtained from aerial parts of the plant. The activity was investigated using acute models of gastric ulcer. Gastric secretion biochemical parameters were determined after pylorus ligature. The participation of cytoprotective factors such as mucus, nitric oxide (NO), sulfhydryl (SH) groups, prostaglandin E2 (PGE 2), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), reduction of lipid peroxidation (malondialdehyde level), and polymorphonuclear infiltration (myeloperoxidase activity), was also investigated. CHCl3P (125, 250, and 500 mg/kg) and AcOEtP (62.5, 125, and 250 mg/kg) showed significant gastroprotective activity, reducing the ulcerative index by 75, 83, 88 % and 66, 66, 81 % for ethanol; 67, 67, 56 % and 56, 53, 58 % for a non-steroidal anti-inflammatory drug (NSAID); and 74, 58, 59 % and 64, 65, 61 % for stress-induced gastric ulcer, respectively. CHCl3P (125 mg/kg) and AcOEtP (62.5 mg/kg) significantly reduced the ulcerative area by 78 and 83 %, respectively, for the ischemia-reperfusion model. They also did not alter the biochemical parameters of gastric secretion, the GSH level or the activities of SOD, GPx or GR. They increased the quantity of gastric mucus, not dependent on NO, yet dependent on SH groups, and maintained PGE2 levels. The P. clematidea phases demonstrated gastroprotective activity related to cytoprotective factors. © 2012 The Japanese Society of Pharmacognosy and Springer.

Avaliação da tolerância de leveduras a um coquetel de inibidores que simula um hidrolisado de bagaço de cana quando adicionado a um meio sintético

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização de filmes finos de YBa2Cu3O7-x e La0.7Ca0.3MnO3 produzidos via síntese química

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação de maçã Royal Gala revestida com filme de quitosana durante o período de pós-colheita

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Utilização so ácido graxo ômega-3 na hipertrigliceridemia de indivíduos com HIV/Aids: relação com níveis de citocinas

Pós-graduação em Doenças Tropicais - FMB

Estudo citocolposcópico anorretal em pacientes com lesões cervicais intraepiteliais de alto grau

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Efeito citotóxico do sistema HRP/Indóis em células McCoy in vitro

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Avaliação de agentes bióticos e abióticos aplicados em pós-colheita na proteção de uva Itália contra Botrytis cinerea

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Desempenho de leveduras que metabolizam xilose para produção de etanol em hidrolisado hemicelulósico de bagaço de cana

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)