Planejamento, síntese e avaliação farmacológica de derivados 1,3,4-oxadiazola-2(3H)-tiona protótipos a fármacos anti-inflamatórios

• Autor(a) principal: Cidade, Amanda Feitosa
• Data de Publicação: 2016
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/6372
• topic: Síntese orgânica; Antinocicepção; Atividade anti-inflamatória; Organic synthesis; Antinociception; Anti-inflammatory activity; CIENCIAS EXATAS E DA TERRA::QUIMICA

The inflammatory process is a defense mechanism of the organism against the noxious stimulus, but if persistent contributes to the pathogenesis of many diseases. As part of a line of research that aims to develop new candidates the prototype anti-inflammatory, we described in this study the planning, the synthesis of derivatives 1,3,4-oxadiazoles-2(3H)-thione (19a-19j) and the evaluation of anti-inflammatory effect of the compound 19f . These compounds were planned from the molecular hybridization strategy from prototype LQFM-021 (12), which presents antinociceptive and anti-inflammatory effect in acute and chronic models, and derivate of the acid flufenamic, a prototype anti-inflammatory inhibitor of the COX-2 and 5-LOX pathway. The synthetic route used to obtain the target compound is effective since it had good yields (22-51%) and obeys the principles of green chemistry. The treatment of mice (n = 8) with the compound 19f reduced the number of abdominals contortions induced by acetic acid, and the antinociceptive action was confirmed in the second phase of the pain test induced by formalin, which allowed differentiate anti-inflammatory activity of this compound of the a analgesic activity. The treatment with compound 19f reduced the edema, in the paw edema model, and anti-inflammatory action it was confirmed by the reduce of the polymorphonuclear cell migration and leukocytes in 43,8% e 61,8 %, respectively, similar to the positive control dexamethasone (60,6% e 74,7% reduction). Was observed the reduction of myeloperoxidase activity (27,8% reduction), in the pleurisy model in mice, and the treatment with 19f was able to reduce the TNF-α concentration in the mice in 56%, dexamethasone positive control reduced in 77,5% compared to the control group. In conclusion we suggest that the anti-inflammatory action of the compound 19f may be associated in the reduction of the TNF-α level. Once the cytokine TNF-α is an important factor in the progression of rheumatoid arthritis, we can infer that the 19f compound show promising profile and can collaborate in the development of new prototypes of drugs related to chronic inflammatory diseases. The pharmacological evaluation of all compounds synthesized this work will serve as a guide to establish the relationship between chemical structure and biological activity of the series (19a-19j), in order for optimize the anti-inflammatory activity.