Lima, Adley Antonini Neves deFerreira, Elayne Barros2020-09-082020-09-082020-06-23FERREIRA, Elayne Barros. Obtenção de sistemas binários com β-ciclodextrina e derivado 2-aminotiofeno para avaliação da atividade antiproliferativa e da toxicidade. 2020. 104f. Dissertação (Mestrado em Ciências Farmacêuticas) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2020.https://repositorio.ufrn.br/jspui/handle/123456789/299602-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), a 2-aminothiophene derivative, has potential pharmacological applicability. However, its physical-chemical characteristics of 6CN impairs its clinical use. This work aimed to develop binary systems between 6CN and β-cyclodextrin (βCD) in order to improve the antiproliferative activity of 6CN in vitro, as well as to reduce its acute and subchronic toxicity in vivo. Molecular modeling and phase solubility studies were performed. The 6CN-βCD binary systems were prepared by physical mixture (PM), kneading (KND) and rotaevaporation (ROTA). After the physical and chemical characterization of binary systems, assays of antiproliferative activity in vitro were performed on normal fibroblast cell lines (3T3), hepatic adenocarcinoma (HepG2) and renal carcinoma (786-0) cells lines. Finally, acute and subchronic toxicity was evaluated in vivo, using only the best system, to assess biochemical, hematological and histopathological parameters. The characterization results show evident changes in the physicochemical properties of 6CN after the formation of the binary systems with βCD.Phase solubility studies indicated that βCD forms stable 1:1 complexes with 6CN, corroborating with the molecular modeling data. The 6CN-βCD binary systems at concentrations of 10 to 50µM, in the MTT assay, showed antiproliferative effects of 20–80% after 48h of exposure to 786-0 and HepG2 cancer cell lines, potentiating the antiproliferative activity of 6CN. In vivo acute and subchronic toxicity tests were conducted with ROTA, in which this binary system reduced the toxicity of 6CN, since there was no mortality for animals treated with this system. The biochemical and hematological findings did not show statistically significant changes indicative of toxicity for animals treated with ROTA. In the histopathological analysis of acute toxicity, hydropic degeneration was observed in the liver of animals treated with only 6CN. Therefore, the association between 6CN and βCD is a useful and promising strategy to improve the physical and chemical characteristics of 6CN. Which May be used in a future safe and effective anticancer therapeutic formulation, since the binary systems increased the cytostatic effect and reduced the toxicity of 6CN.Acesso Aberto6CNDerivados aminotiofenosCiclodextrinasSistemas bináriosAtividade antiproliferativa in vitroToxicidade in vivomasterThesis