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Last Updated: 19/10/2023

Evaluation of compounds with antimalarial potential and study of the GPCR (G-protein coupled receptor) signal transduction mechanism like PfSR25 in Plasmodium falciparum

Objectives

*Original title in Portuguese: Avaliação de compostos com potencial antimalárico e estudo do mecanismo de transdução de sinal do GPCR (G-protein coupled receptor) like PfSR25 em Plasmodium falciparum

This project intends to continue the research studies of antimalarials, unveiling their mechanism of action from the screening of the library of synthetic compounds derived from the 1H and 2H-1,2,3-triazole regioisomers, using the P. falciparum 3D7 and knockout strains for the GPCR-like PfSR25.

Principal Investigators / Focal Persons

Célia Regina da Silva Garcia

Rationale and Abstract

Present in more than 90 countries, malaria is considered the most lethal infectious disease in the world. Epidemiological data released by the WHO recorded more than 228 million cases in 2018, resulting in 405,000 deaths across the planet. The issue of resistance of parasites to antimalarials drives worldwide efforts to discover new drugs with possible inhibitory action on the development of Plasmodium falciparum. This project will use the parasite P. falciparum transgenic GCaMP3 for quantification of cytosolic calcium, and evaluate the impact of triazole compounds in mitochondria of P. falciparum using the construction Mitoemerald-GFP. The potential of these compounds to inhibit the differentiation of asexual stage parasites into gametocytes will also be evaluated using the NF54 strain. These studies also include comparative compound screening between P. falciparum3D7 and PfSR25 knockout strains using the MMV (Medicine for Malaria Venture) library available in our laboratory. It is believed that these studies will contribute to the understanding of the function of the GPCR-like PfSR25 receptor and also to the possible discovery of new drugs with antimalarial activity.

Date

Sep 2020

Project Site

Brazil

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