Learn More
A program was undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a dehydrogenase of the mitochondrial electron transport chain of the malaria parasite Plasmodium falciparum. PfNDH2 has only one known inhibitor, hydroxy-2-dodecyl-4-(1H)-quinolone (HDQ), and this was used along with a range of chemoinformatics methods in the(More)
Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a molecule suitable for further development. In order to reduce ClogP and improve solubility of CK-2-68 incorporation of(More)
The mitochondrial respiratory chain of the malaria parasite Plasmodium falciparum differs from that of its human host in that it lacks a canonical protonmotive NADH:ubiquinone oxidoreductase (Complex I), containing instead a single sub-unit, non-protonmotive Ndh2, similar to that found in plant mitochondria, fungi and some bacteria [1,2]. As such, the P.(More)
Malaria is responsible for approximately 1 million deaths annually; thus, continued efforts to discover new antimalarials are required. A HTS screen was established to identify novel inhibitors of the parasite's mitochondrial enzyme NADH:quinone oxidoreductase (PfNDH2). On the basis of only one known inhibitor of this enzyme, the challenge was to discover(More)
NADH:quinone oxidoreductase (PfNDH2) represents a metabolic choke point in the respiratory chain of Plasmo-dium falciparum mitochondria and is the focus of a drug discovery programme. A miniaturised assay for recombi-nant PfNDH2 with robust assay performance measures was generated for the high throughput screening (HTS) of a focused library of 17,000(More)
  • 1