Banca de QUALIFICAÇÃO: JUSSARA ISA BRAGA PACHECO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : JUSSARA ISA BRAGA PACHECO
DATE: 11/10/2024
TIME: 08:00
LOCAL: Sala Virtual Remota (Microsoft Teams) https://bit.ly/RequalifMSc_JussaraPacheco_PGBIOEXP
TITLE:

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KEY WORDS:

Malaria. Plasmodium falciparum. Naphthoquinones

PAGES: 63
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Malaria, a tropical disease caused by Plasmodium sp. and transmitted by the Anopheles mosquito, accounted for 249 million cases in 2022, with high mortality, particularly in tropical and subtropical regions. Temperature plays a crucial role in transmission, as P. falciparum does not complete its life cycle below 20°C. In the Americas, there has been a significant reduction in cases, with notable declines in Brazil, Colombia, and Venezuela. In Brazil, the majority of cases occur in the Amazon region, with P. vivax responsible for most infections. In 2022, 131,224 cases were reported in the country, with a slight reduction compared to the previous year. The aim of this study is to evaluate the in vitro and in silico antimalarial activity of compounds derived from naphthoquinones, named RM 12, RM 13, and RM 14. To achieve this, the 50% growth inhibition value (IC50) of Plasmodium falciparum W2, the 50% cytotoxic concentration (CC50) in HepG2 (human liver cells) and Vero (monkey kidney cells), and the selectivity index (SI) were determined. Additionally, the hemolytic effect and the physicochemical, pharmacokinetic, and pharmacodynamic properties of the compounds were evaluated using in silico tools. The compounds were obtained and solubilized for further testing. The asexual form of P. falciparum W2 was used, and the results were revealed using the Sybr Green I method, based on a 1:2 serial dilution of the compounds, with an initial concentration of 200 μM. The tests to determine the CC50 value were revealed using the resazurin method. From the ratio between CC50 and IC50, the SI was calculated. Simultaneously, a hemolysis assay was performed using human erythrocytes. Physicochemical properties and biological activities were evaluated using the Osiris and Molinspiration software. In the in vitro study, compound RM 12 showed an IC50 of 5.14 ± 0.5 and a CC50 for HepG2 cells of 32.33 ± 4.88, with an SI of 6.3. Compound RM 13 showed an IC50 of 1.78 ± 0.46 and a CC50 of 221.25 ± 0.74, with an SI of 124.1. As for compound RM 14, the IC50 was 10.77 ± 3.36, the CC50 was 216.9 ± 2.12, with an SI of 20.1. The compounds did not exhibit hemolytic effects, even at higher concentrations. Based on the results obtained, it was concluded that compounds RM 13 and RM 14 were more selective for the parasite. All compounds were active against the parasite; however, compound RM 12 showed higher toxicity. Thus, it is observed that RM 13 is the most active compound and a potential candidate for further preclinical antimalarial tests.

COMMITTEE MEMBERS:
Externo à Instituição - PAULO RENATO RIVAS TOTINO
Externa à Instituição - SARAH EL CHAMY MALUF - USP
Presidente - ***.335.462-** - SORAYA DOS SANTOS PEREIRA - UNIR