Banca de DEFESA: ELAYNE BARROS FERREIRA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : ELAYNE BARROS FERREIRA
DATE: 30/03/2020
TIME: 15:00
LOCAL: SALA 2 DO PPGCF
TITLE:

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

KEY WORDS:

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

PAGES: 117
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

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.

BANKING MEMBERS:
Presidente - 1789788 - ADLEY ANTONINI NEVES DE LIMA
Interna - 2323511 - ADRIANA AUGUSTO DE REZENDE
Externo à Instituição - BOLIVAR PONCIANO GOULART DE LIMA DAMASCENO - UEPB