Potent and selective hydroxynaphthoquinone inhibitors of mitochondrial electron transport in Eimeria tenella (Apicomplexa: Coccidia).
Novel hydroxynaphthoquinones have been shown to be potent and selective inhibitors of mitochondrial electron transport in the protozoan Eimeria tenella, inhibiting at concentrations of 10(-10) to 10(-11)M. The primary site of electron transport inhibition has been localized to the ubiquinol-cytochrome c reductase span of the respiratory chain, whereas a secondary site of inhibition occurs in the NADH- and succinate-ubiquinone reductase complexes. Inhibition at the primary site is selective for the E. tenella enzyme; inhibition at the secondary sites is comparable in both E. tenella and chick (Gallus gallus) liver mitochondria. Hydroxynaphthoquinone inhibition of chick liver succinate-cyto-chrome c reductase was fully reversible by addition of the exogenous ubiquinone-2 analogue, 6-decyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone; inhibition of the corresponding E. tenella enzyme was not reversed by this ubiquinone. E. tenella lines made resistant to the anticoccidial agents decoquinate or clopidol showed no cross-resistance to the hydroxynaphthoquinones, either at the level of electron transport or in vivo.
D003049:Coccidiostats / Q000494:pharmacology*; D004539:Eimeria / Q000187:drug effects* / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone); D009285:Naphthoquinones / Q000494:pharmacology*; D011808:Quinone Reductases / Q000037:antagonists & inhibitors; D013384:Succinate Cytochrome c Oxidoreductase / Q000037:antagonists & inhibitors; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D003049:Coccidiostats; D009285:Naphthoquinones; D013384:Succinate Cytochrome c Oxidoreductase; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases