Banca de QUALIFICAÇÃO: JÉSSIKA DE OLIVEIRA VIANA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : JÉSSIKA DE OLIVEIRA VIANA
DATE: 25/06/2021
TIME: 09:00
LOCAL: https://meet.google.com/cnx-qpud-kwa
TITLE:

In silico design, synthesis and leishmanicidal activity of spiro-acridine derivatives

KEY WORDS:

Leishmania major, Spiro-acridines, PTR1, Inverse Virtual Screening.

PAGES: 69
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Among the neglected diseases, Leishmaniasis has been indicated as the second protozoonosis with the highest mortality rate and prevalence. Linked to this system is the limitation of medications, with low rates of efficacy and safety. In view of this, bioactive compounds have been studied in the literature to offer better efficacy and selectivity against leishmania, representing a promising scenario in the development of drugs against leishmaniasis. Recently an acridine derivative called AMTAC-11 was synthesized and exhibited antileishmania activity against L. infantum, with an IC 50 of 2.6 μM. Based on this, this work aims to identify, by inverse virtual screening based on the structure of the receptor, the probable mechanism of action of acridine derivatives with leishmanicidal activity and to prove through experimental validation. To identify the mode of action of AMTAC-11, in silico and in vitro experiments were carried out. Using an inverse virtual screening approach based on the receptor, the enzyme PTR1 was identified as a potential target. The molecular mooring and molecular dynamics assays demonstrated the high stability of AMTAC-11 at the active site of PTR1, being stabilized by the amino acid residues Phe113, Arg17 and Leu18. Therefore, the present work led to the identification of a new class of LmPTR1 inhibitors and allowed to characterize its potency, inhibition modality and interaction profile with its therapeutic target. Thus, our results suggest that the spiro-acridine derivative AMTAC-11 may be an inhibitor of the enzyme PTR1 in the action antileishmania. However, it is necessary to carry out studies related to the in vitro evaluation of the coupling and inhibition of the AMTAC-11 and AMTAC-9 derivatives for experimental validation of the modulatory mechanism.

BANKING MEMBERS:
Externo à Instituição - EDILSON BESERRA DE ALENCAR FILHO
Externo à Instituição - JAMERSON FERREIRA DE OLIVEIRA
Presidente - 1893445 - EUZEBIO GUIMARAES BARBOSA
Interno - 1837240 - MARCELO AUGUSTO COSTA FERNANDES