Banca de DEFESA: CAÍQUE LOPES DUARTE

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : CAÍQUE LOPES DUARTE
DATE: 29/01/2024
TIME: 14:00
LOCAL: UFSJ
TITLE:

Rational search for a new antimalarial compound

KEY WORDS:

Malaria; Molecular Modeling; N-acylhydrazones; β-carbolines

PAGES: 149
BIG AREA: Ciências Biológicas
AREA: Parasitologia
SUBÁREA: Protozoologia de Parasitos
SPECIALTY: Protozoologia Parasitária Humana
SUMMARY:

Malaria is an infectious disease caused by parasites of the genus Plasmodium.
There are five species that infect humans. The increase in the appearance of
multiresistant strains to the current antimalarial therapeutic arsenal makes it
necessary to search for new biologically active compounds to treat the disease.
The use of molecular modeling techniques has gained prominence in recent
decades for making the drug development process faster and cheaper. This

work evaluated in silico two classes of potential antimalarial compounds, the N-
acylhydrazones and the β-carbolines. The results were generated from

molecular docking calculations against a Plasmodium facilparum target
database, the BraMMT. Of the seven derivatives of N-acylhydrazones evaluated
during in vitro tests, three of them showed activity and were evaluated in silico
for analysis of the mechanism of action. Compound AH5 showed little selectivity
to targets, while AH4 showed greater affinity for the target 3PHC, which is
associated with purine synthesis in the parasite. The other part of the work
evaluated 20 β-carboline derivatives, of which 10 were selected in silico to be
synthesized. Derivatives showed affinity for the 2OK8 target, which is
associated with isoprenoid synthesis. The derivatives selected for synthesis
showed antiplasmodial activity in vitro and later in vivo, and in the latter, they
inhibited the development of cerebral malaria in mice. These results show that
the use of molecular modeling methods can help both in the study of the
mechanism of action of new compounds and in the selection of biologically
active compounds.

BANKING MEMBERS:
Presidente - 1422156 - FERNANDO DE PILLA VAROTTI
Externa ao Programa - 3351249 - SILMARA NUNES ANDRADE
Externa à Instituição - AMANDA LUISA DA FONSECA - UNA