ANTIPLASMODIAL ACTIVITY OF AURORA KINASE-2 INHIBITOR COMPOUNDS FROM PLASMODIUM SPP.

Marcela Lucas Magalhães; Sabrina Silva Mendonça; Luis Carlos Salazar Alvarez; Letícia Tiburcio Ferreira; Joyce Villa Verde Bastos Borba; Bruno J. Neves; Juliana Paim Calit; Daniel Bargieri; Gustavo Capatti Cassiano; Desconhecido1237; Fábio Trindade Costa

Todos os Trabalhos

Trabalho

DOI

10.29327/1275293.1-1

Título do Trabalho

ANTIPLASMODIAL ACTIVITY OF AURORA KINASE-2 INHIBITOR COMPOUNDS FROM PLASMODIUM SPP.

Autores

Marcela Lucas Magalhães
Sabrina Silva Mendonça
Luis Carlos Salazar Alvarez
Letícia Tiburcio Ferreira
Joyce Villa Verde Bastos Borba
Bruno J. Neves
Juliana Paim Calit
Daniel Bargieri
Gustavo Capatti Cassiano
Desconhecido1237
Fábio Trindade Costa

Modalidade

Apresentação de Pôster

Área temática

Imunologia

Data de Publicação

09/06/2023

País da Publicação

Brasil

Idioma da Publicação

Inglês

Página do Trabalho

https://www.even3.com.br/anais/v-gbmeeting/609673-antiplasmodial-activity-of-aurora-kinase-2-inhibitor-compounds-from-plasmodium-spp

ISBN

978-85-5722-785-9

Palavras-Chave

Malaria, Plasmodium, Antimalarials, Aurora kinase

Resumo

Malaria remains a heavy burden on public health and socio-economic in tropical and subtropical regions of the world. The emergence of strains resistant to virtually all recommended treatments highlights the urgent need to identify new antimalarial therapies with new mechanisms of action, emphasizing the need for new strategies in the treatment, prevention, and control of the disease. PfArk-2, a serine/threonine kinase protein related to Aurora, was identified in P. falciparum's kinome and shown to be essential for the parasite's development in different stages of its life cycle. Thus, this target is attractive for the development of new multi-stage antimalarials. The aim of this study was to experimentally validate inhibitors compounds against PfArk-2, based on chemoinformatics strategies based on molecular volume and shape models. Once the computational model was developed and validated, a virtual screening of the ChemBrige commercial library was performed, and a total of six compounds were acquired and tested. SYBR Green fluorimetric assays were used to evaluate in vitro antimalarial activity. The cytotoxicity of the compounds was evaluated through the MTT assay, and inhibition of oocyst conversion was analyzed using the P. berghei Ooluck line. The compounds were initially tested at 5 µM against the 3D7 strain and all showed inhibition above 80%. Among these, EC50 values < 100 nM were observed for the LDT715-720 compounds, both for the 3D7 (chloroquine-sensitive) and Dd2 (chloroquine-resistant) strains. In addition, cytotoxicity assays on COS-7 and HepG2 mammalian cells indicated low toxicity, with IS values > 15, except for LDT720. Additionally, the ability to inhibit in vitro development of oocysts in P. berghei was evaluated, showing that LDT719 and LDT720 have the ability to inhibit over 90% at a concentration of 10 µM. In summary, it was demonstrated that the virtual screening model was successful, leading to the identification of five active compounds (EC50 < 100nM) against P. falciparum, with low cytotoxicity to mammalian cells and potential transmission-blocking properties.

Título do Evento: V GBMeeting
Cidade do Evento: Campinas
Título dos Anais do Evento: Anais do GBMeeting: Encontro Anual da Pós Graduação em Genética e Biologia Molecular da UNICAMP
Nome da Editora: Even3
Meio de Divulgação: Meio Digital
DOI

Como citar

MAGALHÃES, Marcela Lucas et al.. ANTIPLASMODIAL ACTIVITY OF AURORA KINASE-2 INHIBITOR COMPOUNDS FROM PLASMODIUM SPP... In: Anais do GBMeeting: Encontro Anual da Pós Graduação em Genética e Biologia Molecular da UNICAMP. Anais...Campinas(SP) Unicamp, 2023. Disponível em: https//www.even3.com.br/anais/v-gbmeeting/609673-ANTIPLASMODIAL-ACTIVITY-OF-AURORA-KINASE-2-INHIBITOR-COMPOUNDS-FROM-PLASMODIUM-SPP. Acesso em: 21/12/2024