Discovery of Membrane-Bound Pyrophosphatase Inhibitors Derived from an Isoxazole Fragment.
ACS Med Chem Lett
; 11(4): 605-610, 2020 Apr 09.
Article
en En
| MEDLINE
| ID: mdl-32292570
ABSTRACT
Membrane-bound pyrophosphatases (mPPases) regulate energy homeostasis in pathogenic protozoan parasites and lack human homologues, which makes them promising targets in e.g. malaria. Yet only few nonphosphorus inhibitors have been reported so far. Here, we explore an isoxazole fragment hit, leading to the discovery of small mPPase inhibitors with 6-10 µM IC50 values in the Thermotoga maritima test system. Promisingly, the compounds retained activity against Plasmodium falciparum mPPase in membranes and inhibited parasite growth.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_malaria
Idioma:
En
Revista:
ACS Med Chem Lett
Año:
2020
Tipo del documento:
Article
País de afiliación:
Finlandia