Banca de DEFESA: SHEILA CRUZ ARAUJO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : SHEILA CRUZ ARAUJO
DATA : 08/12/2021
HORA: 14:00
LOCAL: https://meet.google.com/wvk-tyju-bzv
TÍTULO:

Identification of inhibitors related to biological targets from Trypanosoma cruzi and drug candidates for Chagas disease´s treatment

PÁGINAS: 145
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Físico-Química
ESPECIALIDADE: Química Teórica
RESUMO:

Chagas disease, more than a century after its discovery, is still a significant public health problem. It is estimated that approximately 10 million people worldwide are infected with T. cruzi, but the situation is more critical in Latin America and other regions where the disease is endemic. The most significant cases occur in Brazil, Argentina, and Mexico, in which there are more than 100 million people in areas at risk for vector contamination. World Health Organization (WHO) has some initiatives to combat the vector to reach 110 million people a year by 2030. The urgent need for new therapeutic alternatives are enormous, since the available drugs have limitations such as low efficacy and high toxicity. Given this scenario, two different approaches were employed in this work: structure-biological activity relationship studies of active derivatives of semi-synthetic neolignans as potential candidates for the treatment of Chagas' disease and virtual screening of a compound database at cruzain and BDF2 that are considered essential for the parasite's survival. In this work, the main objective was to identify drug candidate inhibitors against Chagas disease using different in silico methodologies, as well as in vitro assays. In the first step, we constructed HQSAR, CoMFA, and CoMSIA models from neolignans extracted from Nectandra leucantha´s flowers. Based on the QSAR analyses with 50 natural and semi-synthetic neolignans, it was possible to understand the main structural characteristics related to the biological response of these compounds that help to design new compounds based on neolignans with better biological activity. The second part of this work involved virtual screening of a compound database at the crystallographic structure of cruzain and BDF2, in which pharmacophore filters were used as well as other advanced analyses to select potential bioactive ligands with activity against T. cruzi. Finally, 32 substances were selected, obtained commercially, and submitted to in vitro biological tests against T. cruzi. Of the compounds tested initially, 7 of them presented significant activity against T. cruzi and can be considered as potential drug candidates to treat Chagas disease.

MEMBROS DA BANCA:
Presidente - Interno ao Programa - 149.405.258-05 - KATHIA MARIA HONORIO - USP
Membro Titular - Examinador(a) Interno ao Programa - 1623577 - JOAO HENRIQUE GHILARDI LAGO
Membro Titular - Examinador(a) Interno ao Programa - 1544394 - PAULA HOMEM DE MELLO
Membro Titular - Examinador(a) Externo à Instituição - VINICIUS GONCALVES MALTAROLLO - UFMG
Membro Titular - Examinador(a) Externo à Instituição - HEBERTH DE PAULA - UFES
Membro Suplente - Examinador(a) Externo ao Programa - 1563992 - ANA LÍGIA SCOTT
Membro Suplente - Examinador(a) Externo à Instituição - ALINE THAÍS BRUNI - USP
Membro Suplente - Examinador(a) Externo à Instituição - KAREN CACILDA WEBER - UFPB