Banca de QUALIFICAÇÃO: ELAYNE BARROS FERREIRA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : ELAYNE BARROS FERREIRA
DATA : 07/10/2019
HORA: 09:00
LOCAL: SALA 1 DO PPGCF
TÍTULO:

Characterization and antiproliferative activity of a novel 2-aminothiophene derivative-â-cyclodextrin binary system

PALAVRAS-CHAVES:

6CN. 2-aminothiophene derivative. Cyclodextrins. Binary systems. Anti-proliferative activity. Toxicity in vivo.

PÁGINAS: 107
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), a new 2-aminothiophene derivative, has wide spectrum of pharmacological properties. However, the poor aqueous solubility of 6CN impairs its clinical use. This work aimed to develop 6CN-β-cyclodextrin binary systems with the purpose of increasing 6CN solubility in water and therefore, to improve its pharmacological activity. Computational theoretical studies of molecular modeling and phase solubility diagram were performed. The 6CN-βCD binary systems were prepared by physical mixing (PM), kneading (KND) and rotary evaporation (ROTA). The physical and chemical characterization of binary systems was performed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TG), x-ray diffraction (DRX) and scanning electron microscopy (SEM). In vitro MTT assays investigated the antiproliferative effect of the binary systems and, finally, the in vivo toxicity was evaluated for the system with the best results. The characterization results show evident changes in the physicochemical properties of 6CN after the formation of the binary systems with βCD. In addition, 6CN was associated with βCD in aqueous solution and the solid state, which was confirmed by molecular modeling and the afore mentioned characterization techniques. Phase solubility studies indicated that βCD forms stable 1:1 complexes with 6CN. The 6CN-βCD binary systems at concentrations of 10 to 50 mM, in the MTT assay, demonstrated antiproliferative effects of 20-80% after 48 hours of exposure to carcinogenic cell lines 786-0 and HepG2, enhancing the cytostatic effect of the 6CN, increasing the Antiproliferative activity. In vivo toxicity tests were conducted with the ROTA, in which this binary system reduced the toxicity of the 6CN, since there was no mortality for the animals treated with the system, corroborating the biochemical, hematological and Histopathological. Therefore, binary systems with cyclodextrins emerge as an alternative to overcome the physicochemical limitations of the 6CN, which may be used in a future safe and effective therapeutic formulation.

MEMBROS DA BANCA:
Interno - 2087759 - ANDRE DUCATI LUCHESSI
Externo à Instituição - EDUARDO PEREIRA DE AZEVEDO - UnP
Presidente - 1804884 - VIVIAN NOGUEIRA SILBIGER