Functional screening of selective mitochondrial inhibitors of Plasmodium

International Journal for Parasitology. Drugs and Drug Resistance
Maria G Gomez-LorenzoAlfonso Mendoza-Losana

Abstract

Phenotypic screening has produced most of the new chemical entities currently in clinical development for malaria, plus many lead compounds active against Plasmodium falciparum asexual stages. However, lack of knowledge about the mode of action of these compounds delays and may even hamper their future development. Identifying the mode of action of the inhibitors greatly helps to prioritise compounds for further development as novel antimalarials. Here we describe a whole-cell method to detect inhibitors of the mitochondrial electron transport chain, using oxygen consumption as high throughput readout in 384-well plate format. The usefulness of the method has been confirmed with the Tres Cantos Antimalarial Compound Set (TCAMS). The assay identified 124 respiratory inhibitors in TCAMS, seven of which were novel anti-plasmodial chemical structures never before described as mitochondrial inhibitors.

Citations

Apr 5, 2020·Marine Drugs·María Álvarez-BardónRafael Balaña-Fouce
Aug 28, 2020·Malaria Journal·Sarah El Chamy MalufAdriana Karaoglanovic Carmona
Aug 6, 2019·Molecular and Biochemical Parasitology·Jenni A Hayward, Giel G van Dooren

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Methods Mentioned

BETA
flow cytometry
FCS
Biosensor
Assay

Software Mentioned

SpotfireDecisionSite

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Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.