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.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Johansson NG,Turku A,Vidilaseris K,Dreano L,Khattab A,Ayuso Pérez D,Wilkinson A,Zhang Y,Tamminen M,Grazhdankin E,Kiriazis A,Fishwick CWG,Meri S,Yli-Kauhaluoma J,Goldman A,Boije Af Gennäs G,Xhaard Hdoi
10.1021/acsmedchemlett.9b00537subject
Has Abstractpub_date
2020-02-17 00:00:00pages
605-610issue
4issn
1948-5875journal_volume
11pub_type
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