Bioorganic & medicinal chemistry letters, 2009-02, Vol.19 (3), p.972-975
2009
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Details
- Autor(en) / Beteiligte
- Titel
- Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors
- Ist Teil von
- Bioorganic & medicinal chemistry letters, 2009-02, Vol.19 (3), p.972-975
- Ort / Verlag
- Amsterdam: Elsevier Ltd
- Erscheinungsjahr
- 2009
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Plasmodium falciparum NDH2 (pfNDH2) is a non-proton pumping, rotenone-insensitive alternative enzyme to the multi-subunit NADH:ubiquinone oxidoreductases (Complex I) of many other eukaryotes. Recombinantly expressed pfNDH2 prefers coenzyme CoQ 0 as an acceptor substrate, and can also use the artificial electron acceptors, menadione and dichlorophenol–indophenol (DCIP). Previously characterized NDH2 inhibitors, dibenziodolium chloride (DPI), diphenyliodonium chloride (IDP), and 1-hydroxy-2-dodecyl-4(1 H)quinolone (HDQ) do not inhibit pfNDH2 activity. Here, we provide evidence that HDQ likely targets another P. falciparum mitochondrial enzyme, dihydroorotate dehydrogenase (pfDHOD), which is essential for de novo pyrimidine biosynthesis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0960-894XeISSN: 1464-3405DOI: 10.1016/j.bmcl.2008.11.071Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4422330
- Format
- –
- Schlagworte
- 1-Hydroxy-2-dodecyl-4(1 H)quinolone, Animals, Antibiotics. Antiinfectious agents. Antiparasitic agents, Antiparasitic agents, Biological and medical sciences, Biphenyl Compounds - pharmacology, Chemistry, Pharmaceutical - methods, CoQ, CoQn, DHOD, Dibenziodolium chloride, Dihydroorotate Dehydrogenase, Diphenyliodonium chloride, DPI, Drug Design, Electron Transport, Electrons, Enzyme Inhibitors - pharmacology, HDQ, IDP, Indophenol - pharmacology, Medical sciences, Models, Chemical, NADH Dehydrogenase - antagonists & inhibitors, NADH Dehydrogenase - chemistry, NDH2, Onium Compounds - pharmacology, Oxidoreductases Acting on CH-CH Group Donors - metabolism, Pharmacology. Drug treatments, Phenol - pharmacology, Plasmodium falciparum, Plasmodium falciparum - metabolism, Quinolones - pharmacology, Type II NADH dehydrogenase, Ubiquinone, Vitamin K 3 - pharmacology