A picomolar inhibitor of the Plasmodium falciparum IPP pathway.
Antimicrob Agents Chemother
; 68(8): e0123823, 2024 Aug 07.
Article
em En
| MEDLINE
| ID: mdl-39037239
ABSTRACT
We identified MMV026468 as a picomolar inhibitor of blood-stage Plasmodium falciparum. Phenotyping assays, including isopentenyl diphosphate rescue of parasite growth inhibition, demonstrated that it targets MEP isoprenoid precursor biosynthesis. MMV026468-treated parasites showed an overall decrease in MEP pathway intermediates, which could result from inhibition of the first MEP enzyme DXS or steps prior to DXS such as regulation of the MEP pathway. Selection of MMV026468-resistant parasites lacking DXS mutations suggested that other targets are possible. The identification of MMV026468 could lead to a new class of antimalarial isoprenoid inhibitors.
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Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Antimaláricos
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article