Functional screening of selective mitochondrial inhibitors of Plasmodium

Maria G. Gomez-Lorenzo, Ane Rodríguez-Alejandre, Sonia Moliner-Cubel, María Martínez-Hoyos, Noemí Bahamontes-Rosa, Rubén Gonzalez del Rio, Carolina Ródenas, Jesús de la Fuente, Jose Luis Lavandera, Jose F. García-Bustos, Alfonso Mendoza-Losana

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10 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)295-303
Number of pages9
JournalInternational Journal for Parasitology: Drugs and Drug Resistance
Issue number2
Publication statusPublished - Aug 2018


  • Mitochondrial inhibitors and cytochrome
  • Oxygen consumption
  • Plasmodium falciparum
  • Plasmodium yoelii

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