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Item Planejamento, síntese e avaliação da atividade tipo ansiolítica e do perfil antioxidante de novo candidato a protótipo de fármaco LQFM 180(Universidade Federal de Goiás, 2016-08-26) Braga, Patrícia Caixeta Castro Souza; Costa, Elson Alves; http://lattes.cnpq.br/2607893423583912; Costa, Elson Alves; http://lattes.cnpq.br/2607893423583912; Lião, Luciano Morais; Carvalho, Flávio Silva de; Menegatti, RicardoFaced with the high and increasing number of people suffering from some form of mental illness in the world, it is necessary to develop additional therapeutic options for patients not helped by existing treatments and also to address medical / famacológicas unmet needs. Given this panorama, this paper proposes the design, synthesis and evaluation of pharmacological type anxiolytic activity and antioxidant profile of a new drug candidate prototype 4- (3,5-ditert-butyl-4-hydroxybenzyl) piperazine-1 carboxylate acetate (LQFM180 (8)). The new prototype was designed by molecular hybridisation strategy of prototypes from 4 - ((1-phenyl- 1H-pyrazol-4-yl) methyl) piperazine-1-carboxylate Ethyl (LQFM008 (5)) and 2,6-di- tertbutyl-phenol (BHT (9)). LQFM180 (8) The compound was synthesized by the Mannich reaction, in 92% yield, which was chemically characterized by infrared spectroscopy (IR) and nuclear magnetic resonance dimensional and two-dimensional (1H, HSQC and HMBC). Evaluation of antioxidant status was carried out by cyclic voltammetry, which confirmed that the compound has antioxidant activity. For evaluation central pharmacological activity of the compound were worked four behavioral models in animals, with treatment with LQFM180 at doses of 25, 50 and 100 mmol / kg V.O. In the test of sleep induced by sodium pentobarbital, the LQFM180 (8) reduced latency and increased barbiturate sleep duration, indicating a central depressant activity. Treatment with LQFM180 (8) in different doses did not alter the number of self-cleaning, dung, total and raised intersections, behavioral parameters observed in the open field test; there is no impairment of exploratory activity. Also in the open field test, the compound LQFM180 (8) indicated anxiolytic type activity, demonstrated by the increase in length of stay, and the entrance in the center of the field. LQFM180 (8) treatment did not alter the motor activity test in the chimney, which was evidenced by the animal climbing time. The compound LQFM180 (8) evaluated the maze test in high cross, possess anxiolytic activity type; evidenced by the increase in time and entering the open arms and the time reduction in the central platform. At the end of this work we can see that the synthetic route proposed for obtaining LQFM180 (8) compound was effective, given the high yields obtained, little laborious steps and cost. Finally, we conclude that the employee structural planning was ratified before the success of the structural characterization of the compound and the results obtained from the central pharmacological evaluation in animal models. As perspective, it is necessary to establish the mechanism of action of the molecule as well as the continuation of in vivo evaluations.Item Efeitos vasculares do oleorresina de Pterodon spp. Vogel (Fabaceae) e do seu diterpeno isolado (6α-acetoxi-7β-hidroxivouacapano-17β-oato de metila)(Universidade Federal de Goiás, 2015-06-30) Reis, Carolina de Fátima; Rocha, Matheus Lavorenti; http://lattes.cnpq.br/7459866708740096; Rocha, Matheus Lavorenti; Oliveira, Gisele Augusto Rodrigues de; Ghedini, Paulo CésarThe use of medicinal plants for the treatment of hypertension treatment has been extensively studied. The genus Pterodon spp. Vogel (Fabaceae), popularly known as sucupira, has five native Brazilian cerrado species. Studies demonstrated that the Pterodon spp has antispasmodic and myorelaxant activities. Phytochemical studies of sucupira found furanic diterpenes with vouacapanic skeleton in their fruits, and the therapeutics activities from this gender are essentially attributed to these compounds. The aim of this study was to evaluete the possible vasorelaxant activity and the mechanisms of action of the oil-resin of sucupira (SOR) and its isolated diterpene, methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate in isolated rat aorta preparations. For comparison, verapamil curves (1 nM – 100 μM) were also obtained. The results demonstrated that both, S0R (0 – 56 μg/mL) and the isolated diterpene (0 – 48 μg/mL) have a reversible concentration-dependent vasorrelaxant activity. Endothelium denudation did not impair in the relaxant effect of both, ORS and the diterpene. Aortic rings KCl-stimulated obtained a lower IC50 value than rings contracted with phenylephrine under increasing concentrations of the tested substances. The SOR and diterpene relaxant activity was not impaired when nonselective K+ channels blockers were used (Tetraethylammonium). The use of cyclopiazonic acid (SERCA inhibitor) indicated that there was no involvement of the Ca2+ reuptake by sarcoplasmatic reticulum and the use of ODQ (an inhibitor of guanylyl cyclase) and MDL-12,330A (an inhibitor of adenylyl cyclase), showed that the 3, 5- cyclic guanosine monophosphate (cGMP) and 3',5'-cyclic adenosine monophosphate (cAMP) pathways were not involved in SOR relaxant activity. However, the results indicate a possibly activity of the soluble guanylyl ciclase on diterpene relaxant effect. Both, SOR and isolated diterpene inhibited the CaCl2 induced contractions in aortic rings stimulated with phenylephrine (0.1μM) or Bay K8644 (a Cav1.2 channel activator; 1μM) and by depolarizing KCl solution (40 mM). Computational molecular docking studies demonstrated that the vasodilator effect of diterpene relies on blocking the Cav1.2 channel, and patch clamp results showed that diterpene substantially decreased the ionic current through Cav1.2 in freshly dissociated vascular smooth muscle cells. These findings suggest that SOR and its isolated diterpene induce endothelium-independent vascular relaxation by blocking the L-type Ca2+ channel (Cav1.2).