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. 2009 Feb 1;19(3):972-5.
doi: 10.1016/j.bmcl.2008.11.071. Epub 2008 Nov 24.

Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors

Carolyn K Dong  1 , Vishal Patel, Jimmy C Yang, Jeffrey D Dvorin, Manoj T Duraisingh, Jon Clardy, Dyann F Wirth
Affiliations

Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors

Carolyn K Dong et al. Bioorg Med Chem Lett. .

Abstract

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(1H)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.

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Figures

Figure 1
Figure 1
Chemical structures of (A) DPI, (B) IDP, and (C) HDQ.
See this image and copyright information in PMC

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