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Item Estudo da composição química, de atividades biológicas e microencapsulação do óleo essencial dos frutos de Pterodon emarginatus Vogel - Fabaceae ("sucupira")(Universidade Federal de Goiás, 2012-02-28) ALVES, Suzana Ferreira; CONCEIÇÃO, Edemilson Cardoso da; http://lattes.cnpq.br/7193007113950510; BARA, Maria Teresa Freitas; http://lattes.cnpq.br/3914164125498267The present work aimed to do the study of chemical variability, evaluating biological activities and microencapsulate the essential oil of the fruits of Pterodon emarginatus Vogel (Fabaceae). Chapter 1 presents the study of the chemical variability of essential oil from fruits of sucupira of 11 individual of the Brazilian savanna, collected from five different populations, and were identified as its chemical composition by gas chromatography coupled to mass spectrometry (GC/MS), used for data analysis to multivariate statistical tool that indicated compounds β caryophyllene and α copaene as the main discriminant of the samples studied, both of which are of greater significance. Chapter 2 describes the antimicrobial activity and chemical composition of total oil of the fruits of sucupira, four samples being analyzed, three of the city of Jussara GO and one of region of Jaciara MT. The oils tested showed good antimicrobial activity against bacteria Gram positive (Gram (+)) and moderate activity against Enterobacter aerogenes ATCC 13048. Chapter 3 describes the process of obtaining microcapsules containg essential oil (OE) of sucupira employing the technique of spray drying and the development and validation methodology for quantification of the compound β caryophyllene. Were used gum Arabic and maltodextrin as wall material and prepared five different dispersions (Emulsion 1-E1, Emulsion 2-E2, Emulsion 3-E3, Emulsion 4-E4 and Emulsion 5-E5) which then were atomized in spray dryer. The results show that the drying condition most appropriate was sprinkler beak of 1,2 mm of diameter, power flow the emulsion in system of 4 mL/min, inlet temperature of 160ºC, air flow of 40 L/min e and pressure of 60 psi. Among the emulsions, E2 was standardized with adequate proportion of essential oil and wall materials, by presenting microcapsules (MOE) for having thick-walled, with a pronounced retention of essential oil, spherical morphology and low hygroscopicity. The method developed and validated proved to be linear, precise, acuurate and robust. Chapter 4 presents the evaluation of biological activities of antimicrobial essential oil of PES-01 employing the technique of broth microdilution and antinociceptive and anti-inflamatory activities performed to the microcapsules with the essential oil. The models of pain induced by formalin and hot plate were used to assess the antinociceptive activity and the model of carrageenan-induced pleurisy and Evans blue for evaluation of anti-inflamatory activity. The OE has weak antimicrobial activity (500 μg mL-1) against bacteria Gram (+) and against the fungi of the genus Cryptococcus was inactive against S. aureus ATCC 25923, against bacteria Gram (-) and against the fungi of the genus Candida. OE reduced by 61,54% (300 mg kg-¹) of the reactivity to pain. The MOE reduced 40,87% (1,0 g kg-¹) and 41,57% (2,0 g kg-¹) in first phase of the test formalin-induced pain, suggesting, anti-nociceptive activity. The 2nd phase of the test, the essential oil inhibited 52,35% of the pain related to inflammatory mediators and the microcapsules decreased from 25,86% - 55,60% of the pain. MOE at a dose of 1,0 g kg-¹ showed anti-nociceptive activity in hot plate model, suggestion central analgesic activity. In the arrageenaninduced pleurisy the MOE reduced 25,44% of the complete migration of leukocytes and significantly decreased the concentration of Evans blue in 24,18%, which demonstrates important anti-inflamatory activity.Item Investigação da atividade antitumoral in vitro e in vivo da Eugenia dysenterica DC. (MYRTACEAE)(Universidade Federal de Goiás, 2011-08-30) ANDRADE, Wanessa Machado; PAULA, José Realino de; http://lattes.cnpq.br/3191837532986128; BOZINIS, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018Item AVALIAÇÃO DA TOXICIDADE PRÉ-CLINICA DO LÁTEX E DO EXTRATO ETANÓLICO DAS FOLHAS E DE Synadenium umbellatum PAX.(Universidade Federal de Goiás, 2008-03-12) AZEREDO, Flaubertt Santana de; CUNHA, Luiz Carlos da; http://lattes.cnpq.br/6349547031976679Item Estudo do efeito antinociceptivo e/ou anti-inflamatório das folhas de Spiranthera odoratissima A. St.-Hil. (Manacá). -Possível mecanismo envolvido(Universidade Federal de Goiás, 2010-08-30) BARBOSA, Daniela Borges Marquez; COSTA, Elson Alves; http://lattes.cnpq.br/2607893423583912Spiranthera odoratissima A. St.-Hil. is popularly known as Manacá and it is a native plant of the Brazilian Savanna Cerrado, and it can be found in the states of Mato Grosso, Goiás, Minas Gerais and Bahia. In the folk medicine this plant is used as an appetite stimulant and to treat rheumatism, abdominal pain, headache, muscle pain, stomach and liver dysfunction, kidney infections and urinary retention. The hydromethanolic fraction was obtained from the ethanolic extract of Spiranthera odoratissima leaves. According to phytochemical screening this fraction contains anthraquinones, tannins, flavonoids and coumarins. This fraction showed antinociceptive activity in the acetic acid-induced writhing method and the involvement of central antinociceptive mechanisms was discarded with the hot plate test, since the reduction in the latency to pain was not observed. The major subfraction isolated from the hydromethanolic fraction (sub-Fr10-28) showed antiinflammatory activity in different methodologies. Both hydromethanolic fraction and sub-Fr10-28 contain tannins able to inhibit the activity of phospholipase A2 enzyme, and subsequently inhibiting the production of arachidonic acid and preventing the production of eicosanoids such as prostaglandins, thromboxanes and leukotrienes by lipoxygenase and cyclooxygenase enzymes participation. These eicosanoids are important mediators for the maintenance of inflammatory process. Concluding, the analgesic effect of this plant may be due to an anti-inflammatory action, and this antiinflammatory action could be the result from the blockage of the phospholipase A2 enzyme.Item Caracterização eletroquímica e estudos mecânico-quânticos para obtenção de propriedades eletrônicas de parabenos(Universidade Federal de Goiás, 2011-02-28) BARBOSA, Núsia Luísa; GIL, Eric de Souza; http://lattes.cnpq.br/3218622824233303Parabens are antimicrobial preservatives widely used in the pharmaceutical, cosmetic and food industries. The alkyl side chain connected to the ester group defines some important physicochemical characteristics of these compounds, including the partitioning coefficient and redox properties. The voltammetry and computational analysis were carried out in order to evaluate the redox behavior of these compounds and other phenolic analogues. Correlations between chemical substituents inductive effects of parabens with potential shifts were observed. Using cyclic voltammetry and glassy carbon working electrode, in aqueous, only one single irreversible anodic peak was observed around 0.8 V for methylparaben (MP), etylparaben (EP), propylparaben (PP), butylparaben (BP), benzylparaben (BzP) and phenolic analogues. The positive inductive effect of alkyl groups was demonstrated by the anodic oxidation potential shift to lower values as the carbon number increases and, therefore the parabens (and other phenolic analogues) oxidation processes to the quinoninic forms showed great dependence of substituent pattern. It was further evaluated the influence of pH and composition of supporting electrolyte in voltammetric profile of parabens.Item Estudo fitoquímico e avaliações da toxicidade aguda e atividades biológicas da raiz do vetiver (Vetiveria zizanioides L. Nash) Poaceae(Universidade Federal de Goiás, 2009-03-23) BARROS, Gilvana Cristina de; BARA, Maria Teresa Freitas; http://lattes.cnpq.br/3914164125498267The use of medicinal plants in controlling the diseases has shown its potential for the discovery of new medicines. Among the plant species used in the Hospital de Medicina Alternativa (HMA / SES-GO) highlights the vetiver (Vetiveria zizanioides L. Nash), an aromatic plant of the family Poaceae, used as a mild anti-hypertensive and diuretic. In this work it was investigated the chemical composition of the hydroalcoholic extract of vetiver, the freeze-dried aqueous extract and the essential oil from the roots of V. zizanioides. In the hydroalcoholic extract were found terpenoids compounds and / or saponins, flavonoids and phenolic acid. In the freeze-dried aqueous extract was observed the presence of flavonoids and phenols. In the essential oil 38 compounds were identified, and khusimol, palustrol, khusimona, zizanona and epi-α-vetivona were the major constituents. In the assessment of the acute toxicity of the hydroalcoholic extract and the freeze-dried aqueous extract of root of V. zizanioides, it was concluded that these extracts showed no toxicity at a dose of 2000 mg / kg. The freeze-dried aqueous extract of the roots of V. zizainoides showed no statistically significant diuretic action in the doses tested. In the investigation of antimicrobial activity, the essential oil of the root of V. zizanioides showed potent activity to inhibiting the growth of Staphylococcus aureus with MIC of 0.15 mg / mL. The crude ethanolic extract showed an antimicrobial activity with MIC of 0.19 mg / mL for Bacillus cereus and Micrococcus roseus and 0.39 mg / mL for Micrococcus luteus, S. aureus and Bacillus subtilis. The hexane fraction showed stronger antimicrobial activity against strains of M. luteus, M. roseus, S. aureus and B. cereus. This study could prove that the essential oil, the crude ethanol extract and hexane fraction from roots of V. zizanioides showed antimicrobial potential.Item PRODUÇÃO DE LACASE E BIOCONVERSÃO DE FLAVONÓIDES POR Pycnoporus sanguineus.(Universidade Federal de Goiás, 2009-06-30) BATISTA, Francislene Lavôr; GARCIA, Telma Alves; http://lattes.cnpq.br/6340261924930737; OLIVEIRA, Valeria de; http://lattes.cnpq.br/6300240031300604The bioconversion is an area of the biotechnology that has increased in an expansive way, and it includes enzymatic reactions by microorganisms. These microorganisms that present enzymatic systems similar to those present in mammalian systems, it s the cytochrome P450 (CYP450). That s why the biotransformation an important alternative constitute as models for drug metabolism study. The Pycnoporus sanguineus is a filamentous fungi, basidiomycete of the Polyporaceae family and laccase producer (EC 1.10.3.2), an oxidoreductase enzyme. It was evaluated the influence of flavonoids naringin, naringenin, and quercetin in the growth of P. sanguineus, production of laccase in differents culture media. It was performed various conditions of reaction, such as temperature, agitation and the time of the flavonoids addition. The bioconversion processes were carried out for 24 up to 96 hours and monitored by TLC and HPLC to confirm the existence of potential metabolites. It was used purified laccase of the Pycnoporus sanguineus to evalute the participation of laccase in metabolites of naringin production. Pycnoporus sanguineus developed in differents culture media tested. Naringenin and naringin presented the capability to induce the laccase production by P. sanguineus, whereas quercetin and rutin inhibited the laccase production. The incubation using PDSM did not producted laccase. It was detected several of metabolites, whereas the incubations using quercetin acquired fourteen differents metabolites and the incubations using naringenin producted nine metabolites and naringin producted eight metabolites. In biocatalytic assay under 28ºC and 150rpm using naringin it was not detected the presence of metabolitesItem Estudo da liberação in vitro da progesterona a partir de cáspsulas de gelatina mole: desenvolvimento e validação de método de dissolução(Universidade Federal de Goiás, 2010-06-16) BERRETTA, Mariana de Oliveira; LIMA, Eliana Martins; http://lattes.cnpq.br/7248774319455970Progesterone is a steroid hormone used to treat uterin disfunction, such as hemorrhage and secondary amenorrhea, contraception, hormone replacement therapy in postmenopausal women, as well as in luteal phase support cases in assisted reproduction techniques. However, it presents low oral bioavailability because of its weak water solubility and intense hepatic metabolism. So, progesterone administration is carried out, mainly, through micronized drug dispersed in oils and surfactant formulations, in soft gelatin capsules, trying to improve oral bioavailability. However, there are no official compendia notifications about dissolution methods used to evaluate progesterone release from these dosage forms. Thus, this study proposes progesterone containing soft gelatin capsules dissolution method development and validation aiming to analyze two pharmaceutical specialties (called A and B) in vitro dissolution profile commercially available. Many conditions were evaluated in the study, such as dissolution medium different compositions (pH and surfactant variations), speed of agitation and apparatus (basket, paddle). In this study, reference product A was used as model and ANOVA/Tukey tests were carried out for statistic analysis, with 95% confidence interval. Dissolution method was validated according to selectivity, linearity, accuracy (recovery) and precision parameters. Both products were compared through dissolution profile, release kinetics and dissolution efficiency. Samples quantification was accomplished through high performance liquid chromatography (HPLC), validated through selectivity, linearity, precision, accuracy, detection and quantification limits parameters. Analyzing used conditions, statistic tests, and considering biorelevant characteristics, it was found that dissolution method more appropriate was the one that used paddle, sodium acetate buffer pH 4.5 with 3,0% of sodium lauryl sulfate dissolution medium, volume of 1000 mL, speed of agitation of 150 rpm and temperature of 37° C ± 0,5° C. This method showed to be specific, linear, precise and accurate. After products analysis, it was possible to notice that product B presented the best in vitro performance in the first four hours of test, best dissolution efficiency and that both showed first order kinetics. Quantification method by HPLC was appropriate for analysis, because it showed to be selective, linear, precise and accurate, with detection limit of 44,6 μg/mL and quantification limit of 148,6 μg/mL. Therefore, it is possible to conclude that dissolution method developed and validated showed to be appropriate for analysis, allowing to visualize differences between same batch units and among different pharmaceutical specialties.Item Desenvolvimento e validação de uma metodologia analítica, em CLAE-PDA, para avaliação da estabilidade do 4-nerolidilcatecol na presença de seus produtos de degradação(Universidade Federal de Goiás, 2008-08-20) CARDOSO, Fabiana Fernandes de Santana e Silva; REZENDE, Kênnia Rocha; http://lattes.cnpq.br/3337615895445199The 4-nerolidylcatechol is the main secondary metabolite of the species Pothomorphe umbellata L. Miq. with established antioxidant, anti-inflammatory and photoprotective actions. Nevertheless, after its isolation and storage, evidence of photoinstability is observed, in a way that the characterization of the factors that influence such instability become mandatory, facing the perspective of a new drug development. Therefore, the aim of this paper was to develop and validate a hromatographic methodology able to analyze the degradation kinetic of the 4-NRC, in the presence of the degradation products, using the high performance liquid chromatography coupled to a detector with photodiodes (HPLC-PDA). Our results showed that the analytical method was selective (5 μg/mL) and linear over a wide range of concentrations (5.0 to 500.0 μg/mL) indicating high intra-day (0,02 2.83%) and inter-day precision (0.59 4.89%), besides accuracy (98.46 104.88%) and ruggedness. The photolytic study showed a fast degradation of 4- nerolidylcatechol (tR = 25 min), generating a major product after a total run time of 8 min. The hydrolytic study showed high instability of the substance in alkaline medium (pH 13.00), generating a major product after a chromatographic run time of 26 min. In acid conditions (pH 1.00), the degradation of 4-NRC was slow and partial, even though after 72 hours of exposure, and under heating stress. The main product of the acid degradation was seen after 12 min. The degradation kinetics of 4-NRC in alkaline and photolytic conditions showed evidences of a 2º order profile, for both reactions. Accordingly, it may be proposed the storage of 4-NRC in neutral medium, under refrigerated conditions and also, protected from light incidence preventing degradation. In addition, it must be avoided storage in solution, mainly in alkaline conditions, once they accelerate the rate of 4-NRC degradation.Item Bioconversão e degradação da venlafaxina em seu metabólito ativo(Universidade Federal de Goiás, 2010-03-03) CARNEIRO, Wilsione José; OLIVEIRA, Valeria de; http://lattes.cnpq.br/6300240031300604The venlafaxine, 1-[2-dimethylamino-1-(4-methoxyphenyl)-ethyl] cyclohexanol, is a antidepressant drug of second generation. This is one of the most potent reuptake inhibitor of serotonin and noradrenaline, and its therapeutic effect is attributed to this activity. Venlafaxine is biotransformed in the liver to O-desmethylvenlafaxine (desvenlafaxine), N, O-desmethylvenlafaxine, N-desmethylvenlafaxine. Enzymes CYP2D6, CYP2C19 and CYP2C9 metabolize venlafaxine and major metabolite is the O-desmethylvenlafaxine. This is pharmacologically active and contributes significantly to the pharmacological effect of venlafaxine, as is found in plasma at high concentrations. The investigation of the formation of degradation products is of great importance, because the products formed may be less active, more active or toxic. Bioconversion or the application of microbial models is a strategy to mimic the mammalian metabolism produces significant quantities of metabolites for studies of pharmacological activity and toxicological. This work represents a forced degradation study of venlafaxine extended-release capsules in different stress conditions (acid and alkaline hydrolysis, oxidative and thermal) and select strains of filamentous fungi, to identify those able to metabolize venlafaxine and produce in a semi-preparative major metabolites. The filamentous fungi used were: Aspergillus candidus ATCC 2023, Beauveria bassiana ATCC 7159, Cunninghamella echinulata ATCC 9244, Cunningamella elegans ATCC 6169, Mortierella isabelina ATCC 1757 and Rhizopus arrhizus ATCC 11145. Was developed and validated method stability indicating HPLC using reverse phase for the analysis of venlafaxine in pharmaceutical formulation. The metabolites prepared by bioconversion were used for structural elucidation and later as a reference chemical in the analysis of stability studies and future studies of pharmacological and toxicological activity. The fungus Cunninghamella elegans ATCC 6169 was selected and produced O-desmethylvenlafaxine (desvenlafaxine) and dihydroxy-venlafaxine, similar to those found in mammals, reinforcing the application of microbial models for the study of animal metabolism. The study indicated the stability of the acid condition of venlafaxine, formed two degradation products, the products found were similar to those obtained by bioconversion. The O-desmethylvenlafaxine, corresponds to the active metabolite of venlafaxine in humans and was recently approved for the treatment of major depressive disorder. Those studies, one can get the O-desmethylvenlafaxine in bioconversion reactions by Cunninghamella elegans ATCC 6169 and forced degradation studies of venlafaxine. The method developed and validated HPLC method was considered indicative of stability analysis of venlafaxine extended-release capsules, it is sensitive, specific (interference < 2%), precise (RSD < 2%), linear (r > 0.99), accurate (98.0 to 102.0%) and reproducible (RSD < 2%).Item Obtenção e Caracterização do Extrato Seco Padronizado da Rosmarinus Officinalis L. (Lamiaceae)(Universidade Federal de Goiás, 2011-02-24) COUTO, Renê Oliveira do; CONCEIÇÃO, Edemilson Cardoso da; http://lattes.cnpq.br/7193007113950510; PAULA, José Realino de; http://lattes.cnpq.br/3191837532986128In this work, standardized spray-dried extracts of Rosmarinus officinalis L.(Lamiaceae), were obtained. The work started with the obtainment and characterization of the R. officinalis dried and powder leaves. A hydroalcoholic extract was obtained by percolation using as solvent ethanol at 80 % (v/v). The drying experiments followed a Box-Behnken (33) factorial design in order to obtain dry powders with optimized properties. In this way, the influence of several in-process parameters e. g. extract feed rate, drying air inlet temperature and spray nozzle airflow rate, on the dried extracts properties were investigated. The herbal raw material as well as both hydroalcoholic and dried extracts were analyzed by several physic-chemical and physical techniques. Additionally, the in vitro antioxidant activity from both hydroalcoholic and dried extracts were assessed by DPPH free radical scavenging test. Rosmarinic acid, the major component on the specie and one of the main compounds responsible for these pharmacological activities, was used as chemical marker in High Performance Liquid Chromatography (HPLC) coupled to photodiode array detection (PDA) quantification assays in all steps of this work. The analytical method was validated following Agência Nacional de Vigilância Sanitária (ANVISA Brazilian National Health Surveillance Agency) guidelines. This method proved to be simple, rapid, selective, linear, sensible, precise, accurate a robust. On the herbal raw material characterization, it were observed a swelling índex of 2.33 ± 0.11, a mean powder size of 437.94 ± 7.00 μm, as well as moisture, total ashes, acid insoluble ashes, total polyphenols, total tannins, total flavonoids and rosmarinic contents of 9.1 ± 0.23, 7.32 ± 0.045, 0.378 ± 0.016, 3.81 ± 0.043, 0.49 ± 0.01, 1.73 ± 0.07 and 1.05 ± 0.03% (w/w), respectively. The concentrated hydroalcoholic extract presented density of 0.964 ± 0.002 g/mL, solids content of 9.66 ± 0.07%, pH 5.106 ± 0.005, alcoholic content of 38.2 ± 0.53% and a viscosity of 5.2 ± 0.09 mPas. The levels of total polyphenols, total tannins, total flavonoids and rosmarinic contents were of 30.19 ± 0.24, 9.13 ± 0.01, 8.78 ± 0.1 and 10.68 ± 0.43% (w/w), respectively. Also, in the antioxidant assessment, the extract presented an inhibitory concentration (IC50) of 17.29 μg/mL. Results showed drying yields ranging from 17.1 to 74.96%. Also, all dried products showed moisture contents and water activities below 5% (w/w) and 0.5, respectively. Although dry products having lost some of their polyphenols they still presented antioxidant activities (IC50) ranging from 17.58 to 24.83 μg/mL. However, most recovered products presented inadequate flowability and compressibility. In general, the particles showed spherical shape and various sizes. Analysis of variance (ANOVAs) proved that the factors studied and some of their interactions significantly affected most of the investigated responses. Moreover, the best condition for obtaining dry extracts of rosemary with stability evidence as well as adequate physicochemical and functional properties is the one performed with a high extract feed rate, an intermediate drying air inlet temperature and a low spray nozzle air flow rate. Accordingly, spray drying technique may be an attractive and promising alternative to develop intermediate phytopharmaceutical products of rosemary.Item Produção e caracterização da atividade de tirosinase no extrato bruto de Pycnoporus sanguineus CCT-4518(Universidade Federal de Goiás, 2009-07-15) DUARTE, Livia Teixeira; SANTIAGO, Mariângela Fontes; http://lattes.cnpq.br/7143224488081563; BARA, Maria Teresa Freitas; http://lattes.cnpq.br/3914164125498267Tyrosinase (E.C.1.14.18.1) is an enzyme of industrial interest that catalyses the ohydroxylation of monophenols (monophenolase activity) and the oxidation of o-diphenols to reactive o-quinones (diphenolase activity), both reactions using molecular oxygen. Pycnoporus sanguineus (L. ex Fries) Murril, is a white rot fungi capable of producing tyrosinase and widely distributed in nature. It is found in regions of mild climate and in tropical forest. The production and characterization of tyrosinase from P. sanguineus were investigated. The selection of inductors, determination of the luminosity influence, biomass and culture media in the production of tyrosinase and the effect of inhibitors on enzyme activity were determined. The fungus produced intracellular tyrosinase and the higher activity was observed using 0.15% L-tyrosine as inducer, in the presence of light, with inoculum of 10 mycelium discs, medium malt extract broth 2%, incubation at 30°C, and constant agitation of 150 rpm, during 2 days. 6 mmol.L-1 salicylhydroxamic acid (SHAM) and 6 mmol.L-1 phenylthiourea (PTU) inhibited 100% of the tyrosinase activity. 0.1 mmol.L-1 sodium azide inhibited 4.15% of tyrosinase activity, while no inhibition was observed after addition of 0.1 mmol.L-1 of phenylmethanesulfonyl fluoride (PMSF). Using L-dopa as substrate, the intracellular crude extract presented optimum pH of 6,6, optimum temperature of 45°C, low stability at 50°C, maintaining about 50% of the activity after 15 min of incubation. The tyrosinase production was confirmed by non-denaturing polyacrylamide gel electrophoresis, using commercial fungal tyrosinase as positive controlItem Planejamento, síntese e avaliação farmacológica de novos candidatos a protótipos de fármacos anti-inflamatórios(Universidade Federal de Goiás, 2009-06-15) GOMES, Marcelo do Nascimento; MENEGATTI, Ricardo; http://lattes.cnpq.br/8354030864254626In the field of a research line that seeks the planning, the synthesis and the pharmacologycal evaluation of new candidates to prototypes of anti-inflammatory drugs, we will describe in this project the planning of derived new pyrazolics (LQFM 002-003), originally drawn starting from the nerolidilcatecol (24) and arylsulfonilpiperazines, (25) that present profile inhibition of the enzyme sPLA2. The compounds (E)-N-(3,7-dimethylocta-2,6-dienyl)-1,3-dimethtyl-1-H-pyrazol-5-amine (LQFM 002) and (E)-N-(3,7-dimethylocta-2,6-dienyl)-1,3-dimethyl-4-((4-methylpiperazin-1-il) methyl)-1H-pyrazol-5-amine (LQFM 003), were submitted to pharmacologycal rehearsals in vitro, seeking to evaluate the enzymatic inhibition activity of the sPLA2. For the prototype (LQFM 002) the inhibition halos were 14,43 ± 6,28%, 16,68 ± 2,45%, 23,61 ± 2,62%, 37,06 ± 3,25%, in the doses of 250, 500, 1000 and 2000 μg/mL respectively. For the compound (LQFM 003), the halos were 1,85 ± 1,38%, 9,29 ± 3,33%, 7,82 ± 3,32%, 13,21 ± 3,22%, respectively. Subsequently the rehearsal in vivo was accomplished to evaluate the profile of cellular migration. Being also analyzed the concentration of plasmatic protein by the methodology of the Evans of blue once the inflammatory process was induced. The compound (LQFM 002) presented inhibition on cellular migration of 50,46 ± 14,34% in the peritonit test, 68,7 ± 2,65% in the pleurisy test and reduction of 40,1 ± 6,40% of the plasmatics proteins for the method of coloration of the Evans of blue. The compound (LQFM 003) presented 25,89 ± 5,39% inhibition, in the doses of 50 mg/Kg, characterizing, significant anti-inflammatory profile for the prototype (LQFM 002). Parallel to the pharmacologycal synthetic work and, we carried out theoretical studies through the application of molecular dynamics. The parameters of the enzyme sPLA2 was more effective through the applications of the water box's, once the smaller state energy observed was of -175000kcal/mol. At the end of this project, we can conclude that the structural planning applied in the project was validated through the applications of the pharmacologycal rehearsals, once both molecules were recognized by the enzyme sPLA2 and they presented anti-inflammatory activity in the rehearsal of cellular migration. In addition, the applied synthetic methodology for obtaining of the prototypes pyrazolics (LQFM 002-003) studied was satisfatory.Item Cromatografia em camada delgada acoplada a voltametrias cíclica e de pulso diferencial na análise de ácido rosmarínico de Rosmarinus officinalis Linné (Alecrim)(Universidade Federal de Goiás, 2010-12-06) GONÇALVES, Darlene; CONCEIÇÃO, Edemilson Cardoso da; http://lattes.cnpq.br/7193007113950510; GIL, Eric de Souza; http://lattes.cnpq.br/3218622824233303This study shows a solid-state electroanalytical method for identification and quantification of rosmarinic acid (RA), a phytoantioxidant of great interest for its therapeutical advantages and applicability in food, cosmetics and pharmaceuticals areas; after it had been isolated from Rosmarinus officinalis Linné (rosemary) samples through thin layer chromatography (TLC), then the silica containing the isolated analyte (chromatographic stain) scraped from chromatographic plates was used to prepare carbon paste electrodes, which were subjected to analysis by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The proposed method showed excellent analytical potential, low cost, speed, ease of implementation and linearity, which can also be applied to other phytoantioxidants in quality control practices of herbal drugs, contributing to the evaluation and quality assurance of them.Item Aplicação De Fungos Filamentosos Na Β-Glicosilação Da Entacapona(Universidade Federal de Goiás, 2011-02-25) LUSTOSA, Keyla Rejane Magno Dias; OLIVEIRA, Valeria de; http://lattes.cnpq.br/6300240031300604The study of bioconversion of biologically active compounds by microorganisms, mainly filamentous fungi and their possible glycosylated derivatives have been extensively explored and have brought promising results. Microbial models of animal metabolism, based on the similarity of the hepatic metabolism and microbial enzyme, became an alternative for the elucidation of metabolic routes of both drugs as well as new drug candidates. In this context, the objective of this study was to explore the ability of filamentous fungi to promote the bioconversion of entacapone and perform the identification, purification and characterization of derivatives formed. We selected eight filamentous fungi Absidia blakesleana ATCC 26617, Aspergillus candidus ATCC 1009, Beauveria bassiana ATCC 7159, Beauveria sp, Cunninghamella echinulata ATCC 9244, Cunninghamella echinulata ATCC 9245, Cunninghamella elegans ATCC 26169 and Rhizopus arrhizuz ATCC 11145, six of them proved to be effective in the metabolism of entacapone, Cunninghamella echinulata ATCC 9245 being the most promising. Were detected 5 different functionalized derivatives, one of which the majority was characterized by Nuclear Magnetic Resonance of Carbon (13C NMR) and Hydrogen (1H NMR), High-Performance Liquid Chromatography coupled to Mass Spectrometer (HPLC-MS/MS) and Infrared Spectroscopy (IR) as a β-glycosylated derivative of entacapone (E, Z): 4 hydroxy-5-nitrophenyl-3-O-(β)-D-glucopyranose-(E)-2-cyano-N, N-diethyl-3-acrylamide.Item Avaliação do relaxamento vascular induzido por um novo derivado pirazólico protótipo a fármaco (LQFM 021), possível inibidor de fosfodiesterase(Universidade Federal de Goiás, 2012-02-28) MARTINS, Daniella Ramos; ROCHA, Matheus Lavorenti; http://lattes.cnpq.br/7459866708740096The inhibition of phosphodiesterases (PDEs) increases intracellular levels of cyclic nucleotides 3 ': 5'-cyclic adenosine monophosphate (cAMP) and 3 ': 5'-cyclic guanosine monophosphate (cGMP), which has many physiological and biochemical effects, especially in cardiovascular system. The objective of this study was to analyze the pharmacological effects of a new compound derived from pyrazole, LQFM 021, which was indicated by molecular modeling studies as a possible inhibitor of PDE-3. For this purpose, aortas were isolated of rats and mounted in organ baths for isometric tension recording of the relaxing effect of LQFM 021, in preparations pre-contracted with phenylephrine. We analyzed the involvement of the vascular endothelium, soluble guanylate cyclase (sGC) and adenylate cyclase (AC), the role of K+ channels and Ca2+, besides the contribution of Ca2+ uptake by the sarcoplasmic reticulum. As a result, was demonstrated that the LQFM 021 induces vascular relaxation (Emax: 54.9 ± 6.0%), being this relaxation potentiated by endothelium (Emax: 88.1 ± 2.1%). The inhibition of AC with MDL-12.330A (10 μM) or of the sGC with ODQ (1 μM) reduced the relaxation of 88.1 ± 2.1%, to 48.35 ± 3.01% and 19.95 ± 2.32%, respectively. The pre-contraction with KCl 45 mM or treatment of preparations with TEA (5 mM), reduced almost completely the relaxing effect of the compound. Inhibition of Ca2+ / ATPase reticular with CPA (10 mM) reduced the relaxation stimulated by 021 LQFM approximately 66.5%. Concentration-response curve contractile induced by phenylephrine (0.1 nM to 1 μM) or by CaCl2 (0-3 mM, zero-calcium + phenylephrine) were reduced by pretreatment of preparations with LQFM 021 (EC50). In conclusion, this study showed that the new synthetic derivative of pyrazole LQFM 021 is a potential inhibitor of PDE-3 and has vasorelaxant activity. The endothelium potentiates the relaxation stimulated by the compound. The route of sGC and AC are involved in the mechanism of action of LQFM 021. Was also evidenced by participation from sarcoplasmatic reticulum, well as the flow of K+ and Ca2+ through the cell membrane.Item Planejamento, síntese e avaliação farmacológica de novos candidatos a protótipos de fármacos anti-inflamatários, desenhados a partir do nerolidilcatecol(Universidade Federal de Goiás, 2009-09-18) MARTINS, Fabiula Ines; SABINO, José Ricardo; http://lattes.cnpq.br/9101677399031185; MENEGATTI, Ricardo; http://lattes.cnpq.br/8354030864254626Inflammation is a local reaction of tissue involving neurological, vascular, humoral and cellular reactions to eliminate the causal agents and reduce the cellular damages. Prostaglandins, thromboxanes and leukotrienes are examples of chemical inflammation mediators, resulting for the action of the enzyme phospholipase A2 (PLA2). The PLA is a enzyme that hydrolyses membrane phospholipids in the sn-2 position resulting in lisophospholipids and arachidonic acid (AA), taking a key role in the production of lipidic inflammatory mediators. The research and development of new chemical entities security, effective and that presents less side effects to the particular therapeutic target, constituted the principal objective of technological innovation in pharmaceuticals industry. Due the side effects of selective inhibitors of the production of eicosanoids currently presents in the market, control of production of AA by inhibiting PLA2 is a useful treatment for pathological conditions that are caused by mediators of the AA. In this work synthetic routes were studied to obtain new candidates prototypes of anti-inflammatory drugs obtained by rational planning of new piperazines derivatives originally designed from nerolidylcatechol (25) and arilsulfonilpiperazines (26) to presents the inhibitory profile of secreted PLA2 enzyme. The final synthesized compound, N-(benzo[d][1,3]dioxol-5-aryl) acetamide (18), E-N-(3,7-dimetylocta-2,6-dienyl) benzo[d] [1,3]dioxol-5-amine (19), (E)-N-(6-dienil,3,7-dimetilocta-2)aminobenzeno (20), (E)-4-(6-dienil,3,7-dimetilocta-2)(aminometil)fenol (21) e (E)-(N)-(6-dienil,3,7-dimetilocta-2)-N-(4-idroxifenil)metanosulfanoamida (22) were submitte to in vitro pharmacological assays to evaluated the enzymatic inhibition of sPLA2 and characterization by hydrogen nuclear magnetic resonance (RMN 1H) and the 13 carbon nuclear magnetic resonance (RMN 13C). Based on the obtained results by pharmacological assays can be concluded that the final synthesized compounds (18, 19, 21, 22) presents good anti-inflammatory profiles. As the synthetic methods employed to obtain the final molecules (18-22) the results showed be viable in its execution enable an obtainment of compounds with appropriate yields and efficiency in the profile of purificationItem Investigação da mielotoxicidade e do potencial indutor de morte celular de Synadenium umbellatum Pax. em células do tumor ascítico de Ehrlich(Universidade Federal de Goiás, 2010-03-03) MOTA, Mariana Flávia da; BOZINIS, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018In search of new antineoplasic agents natural products have played an important role, given that about 40% of available medicines in current treatments have been developed from natural sources, 25% approximately of plants. Synadenium umbellatum belongs to Euphorbiaceae family and is popularly known as "cola-nota", "avelós," "milagrosa", "cancerola", and the latex is empirically used in Brazil for the treatment of cancer. Preliminary studies have shown that the crude extract of the leaves of S. umbellatum has significant antitumor and antiangiogenic activity in vivo. In this study, we investigated the cytotoxicity and the mechanisms of apoptosis induction of S. umbellatum in Ehrlich ascitic tumor (EAT) cells, and the myelotoxic potential of this plant. The cytotoxicity studies were carried out by trypan blue exclusion and reduction of tetrazolium (MTT) tests. The mechanisms of apoptosis induction were investigated by light and fluorescence microscopy, immunocytochemistry and flow cytometry. Investigation of the myelotoxic potential was performed by clonogenic assay of colony forming units of granulocyte-macrophage (CFU-GM). The data were analyzed by analysis of variance (ANOVA) and a posteriori Tukey test (myelotoxicity) and by t test for all other assays. The means were considered statistically significant when P < 0.05. S. umbellatum was cytotoxic to EAT cells and the morphological analysis of these cells indicated that the plant extract treatment induced cell death by apoptosis. Apoptosis was also observed by increase on reactive oxygen species generation and in the concentration of intracellular Ca2+, alterations in mitochondrial membrane potential, phosphatydylserine externalization and activation of caspases 3, 8, and 9. S. umbellatum presented myelotoxicity to normal bone marrow cells in a concentrationdependent fashion. However, this toxicity was 8-fold lower than to tumor cells. The presented data showed that S. umbellatum had cytotoxic activity to EAT cells and induced these cells to apoptosis.Item Planejamento e síntese de intermediários para a obtenção de novos candidatos a protótipos de fármacos anticoagulantes desenhados a partir da infestina-4(Universidade Federal de Goiás, 2010-09-15) NASSAU, Laura Maia Mairink; CAMPOS, Ivan Torres Nicolau de; http://lattes.cnpq.br/5450204304438682; MENEGATTI, Ricardo; http://lattes.cnpq.br/8354030864254626Thromboembolic disorders produce the majority of diseases affecting the heart, and are the third leading cause of death worldwide. Venous thromboembolism is a thromboembolic disorder that occurs in the venous circulation, is a disease of high prevalence and remains a major cause of morbidity and mortality in hospitalized patients undergoing major surgery, the fact that affect patients from the very young, disease free prior to the more elderly mean that it is a problem with major socioeconomic burden by as much as by absenteeism in hospital patients in productive age. This describes the planning and synthesis of intermediates for the collection of new derivatives guanidine drawn from the infestina-4, protein extracted from the stomach Barber Triatoma infestans, with potent inhibitory activity of factor XII. Factor XII acts of direct and indirect enzymatic cascades in four of our body and has an important contribution to the formation of pathological vascular thrombi. The previous study of molecular modeling justified based planning in the structural and the electrostatic infestin. Thus it is concluded that the synthesis of intermediates 25-28, were getting adequate yields of 88.0 and 92.0% for compounds 25 and 26 and 71.4 and 65.0% for compounds 27 and 28 respectively.Item Obtenção e Caracterização do Extrato Seco Padronizado dos Frutos da Sucupira Pterodon emarginatus Vogel, Fabaceae(Universidade Federal de Goiás, 2010-08-31) OLIVEIRA, Patrícya Caixeta de; CONCEIÇÃO, Edemilson Cardoso da; http://lattes.cnpq.br/7193007113950510; BARA, Maria Teresa Freitas; http://lattes.cnpq.br/3914164125498267The Pterodon emarginatus Vogel, known as sucupira branca (Fabaceae) has been shown to possess larvicidal activity against (Aedes aegypti), antiparasitic effect (Leishmania amazonensis), fungicide, bactericide, antioxidant, antiinflammatory, antinociceptive, and antiproliferative activity among several different human cancer cell lines that may be related to presence of diterpenes, in particular, vouacapanes derivatives. This work aimed to define and characterize the powder, the crude and standardized dry extract of the fruit of sucupira . After crushing the fruits, showed 1.2% volatile. The chromatographic (TLC) indicated the presence of chemical markers vouacapanes (6α,7β-dihydroxyvouacapan-17β-oic acid - Rf = 0.16; 6α,7β-dihydroxyvouacapan-17β-oate methyl ester - Rf = 0.44; 6α-hydroxyvouacapan-7β-17β-lactone - Rf = 0.71) and lupeol (Rf = 0.78). In vibration bands in the infrared region coinciding with the five main bands of vouacapanes (-OH, C-H , C=O, C=C, C-O). The concentration of total terpenes of 9.3%. Then to obtain the crude extract was held percolation in 95% ethanol PA. The crude extract showed pH 5.1, relative density of 0.87, viscosity of 25.43 mPas, solid 15.2%, total terpenes of 17.1% and the same chromatographic profile and in the infrared spectrum obtained for the powder plant. Another method used for investigation of terpenes was the gas chromatography / mass spectrometry in the hexane extract. We identified the presence of vouacapanes and the lupeol. The drying process of the crude extract was used nebulization (spray drying) using different adjuvants drying, flow of 0.19 L / h, air flow 35 L / min, inlet temperature 110°C, outlet temperature 97°C, double fluid nozzle spray type 1.2 mm. The best results were obtained with the colloidal silicon dioxide (Aerosil®) to 20%, giving an appearance of fine powder. Thermal analysis performed for the marker 6α,7β-dihydroxyvouacapan-17β-oate methyl ester showed that the drying parameters were safe by preventing the thermal degradation of diterpenes. The efficiency of the drying process was 16.2%, degradation of 10.9% and the concentration of terpenes total in dry extract was 13.9%. The chromatographic profile was maintained and the volatile content was 3.5%. The photomicrographs showed irregular and spherical particles, rough surface. The analytical method by spectrophotometry in the visible region for the quantification of total terpenes in the dust, crude extract and dry extract was validated presenting selective, linear, precise, accurate and robust. In the test of antinociceptive activity (capsaicin), the pre-treatment with dry extract of sucupira (SDE 1000 mg / kg + 20% DMSO) reduced the time reactivity in 50.9% compared to the vehicle. The results may suggest that the technological processes employed to transform the fruits of sucupira in standardized dry extract was adequate to maintain quality chemistry and antinociceptive activity described for the fruits. This work represents the first description of the taking of standardized dry extract and identification of lupeol in fruits of sucupira .