Planejamento, síntese e avaliação da atividade tipo ansiolítica e do perfil antioxidante de novo candidato a protótipo de fármaco LQFM 180
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2016-08-26
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Universidade Federal de Goiás
Resumo
Faced 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.
Descrição
Palavras-chave
Síntese orgânica medicinal , Derivado piperazínico , Fármacos antioxidantes , Avaliação farmacológica , Tratamento de ansiedade patológica , LQFM180 (8) , Medicinal organic synthesis , Derived piperazine , Antioxidants drugs , Pharmacological evaluation , Treatment of pathological anxiety , LQFM180 (8)
Citação
BRAGA, P. C. C. S. Planejamento, síntese e avaliação da atividade tipo ansiolítica e do perfil antioxidante de novo candidato a protótipo de fármaco LQFM 180. 2016. 56 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2016.