Obtenção de sistemas binários com β-ciclodextrina e derivado 2-aminotiofeno para avaliação da atividade antiproliferativa e da toxicidade
2-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 (βC...
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| Formato: | Dissertação |
| Idioma: | pt_BR |
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Universidade Federal do Rio Grande do Norte
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/29960 |
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| Resumo: | 2-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. |
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