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 mu M IC50 values in the Thermotoga maritima test system. Promisingly, the compounds retained activity against Plasmodium falciparum mPPase in membranes and inhibited parasite growth.

Original languageEnglish
JournalACS Medicinal Chemistry Letters
Volume11
Issue number4
Pages (from-to)605-610
Number of pages6
ISSN1948-5875
DOIs
Publication statusPublished - 9 Apr 2020
MoE publication typeA1 Journal article-refereed

Fields of Science

  • ACIDOCALCISOMES
  • BISPHOSPHONATES
  • Membrane-bound pyrophosphatase
  • PUMPING PYROPHOSPHATASES
  • TARGET
  • TRYPANOSOMA-BRUCEI
  • drug design
  • isoxazoles
  • protozoan diseases
  • 317 Pharmacy

Equipment

Viikki Metabolomics Unit - ViMU

Nina Sipari (Manager)

Facility/equipment: Equipment

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