Banca de DEFESA: SOFIA SANTOS DA SILVA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : SOFIA SANTOS DA SILVA
DATE: 11/02/2021
TIME: 14:00
LOCAL: VIDEOCONFERÊNCIA (SESSÃO FECHADA)
TITLE:

In silico understanding of the inclusion complex formation, obtention and physico-chemical characterization of Bztempo and β-cyclodextrin system to the treatment of Chagas Disease

KEY WORDS:

Bztempo, nitroxides, beta-cyclodextrin, inclusion complexes

PAGES: 73
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

The free radicals produced to the maintenance of Trypanossoma cruzi’s (T. cruzi) infection in the human, under the chronic phase of Chagas Disease has a direct relation with the development of cardiomyopathies and antioxidants are being used as allies to the treatment of this condition. Nitroxides are stable free radicals that can interact with reactive species, reducing its load in the organism and, consequently, acting in the reduction of the corporal oxidative stress. Tempol is the most studied nitroxide and, through the addition of functional groups, other molecules can be obtained, such as Bztempo (BZT). The inclusion complexes with β-cyclodextrin (βCD) can be obtained to enhance the physicochemical properties and bioavailability of many compounds. Thus, the following study aims to rationally achieve an inclusion complex with BZT and βCD to the treatment of the infection by T. cruzi. The inclusion complexes were planned by two in silico methodologies, Quantitative Structure-Property Relationship (QSPR-2D) and Linear Interaction Energy (LIE). The systems were achieved by physical mixture (PM), kneading (KN) and slurry (SL) methods, and characterize by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). The in vitro activity was made by resazurin’s inhibition in two T. cruzi’s evolutive forms (Y strain) facing the samples of BZT, βCD, KN and SL. The prediction model achieved by QSPR-2D method, allied to LIE, was capable to indicate the viability of the inclusion complexes between BZT and βCD, showing favorable free-energies to the interaction between the compounds. The FTIR results have indicated the inclusion complexes formation by KN and SL, due to the differences shown in their spectra related to the isolated compounds. The photomicrographs achieved by SEM presented indicatives of the inclusion complex formation due to the changes in the surface of the systems, comparing to the isolated samples. The DSC of the systems achieved by PM and KN methods has exhibited characteristic endothermic events of the isolated compounds. By other hand, the SL has shown a thermal profile that differs from the isolated compounds, with characteristic events of the mixture itself. The TGA has shown that KN and SL samples have enhanced the thermal protection of the BZT. Regarding the in vitro activity, the βCD has not interfered in the activity of the both evolutive forms and, the testes systems, KN and SL, had increased the activity of isolated BZT. To the epimastigote forms, KN and SL hasn’t reached close results to the positive control drug, Benzonidazole (BZND). To this evolutive form, KN complex had a better activity in comparison to SL until the concentration of 50 μg/mL, and after this concentration, the SL had a better activity. To the trypomastigotes, KN had a similar activity to BZND in the concentrations of 10 and 25 μg/mL. In 50, 100 and 1 μg/mL, the KN has stand out in relation to BZND, and to the other system achieved, SL. The results have shown that the inclusion complexes achieved with BZT by KN and SL can be allies in the treatment of Chagas Disease.

BANKING MEMBERS:
Externo à Instituição - ADRIANO ANTUNES DE SOUZA ARAÚJO - UFS
Interna - 1218940 - ANTONIA CLAUDIA JACOME DA CAMARA
Presidente - 1893445 - EUZEBIO GUIMARAES BARBOSA