The inhibition by a series of potentially bioreductive naphthoquinones of rat liver mitochondria and sarcoma 180 tumor cell respiration.
A series of potentially bioreductive naphthoquinones were investigated for their effects on rat liver mitochondrial electron transport and energy transfer and their ability to inhibit Sarcoma 180 tumor cell respiration in vitro. It was found that all the naphthoquinones evaluated, inhibited tumor cell respiration and rat liver mitochondrial oxidative metabolism. It was also found that 1,4-naphthoquinones substituted at the 2 and 3 positions were more effective inhibitors of the respiratory and energy transfer systems studied than those substituted at the 2 position only. 2,3-bis(chloromethyl) 1,4-naphthoquinone was found to cause the most rapid onset of inhibition, cause an immediate burst of cyanide insensitive respiration, and cause a preferential reduction of cytochromes c, a and a3 following oxygen depletion.
D000818:Animals; D002417:Cattle; D003580:Cytochromes / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D012510:Sarcoma 180 / Q000378:metabolism*
D003580:Cytochromes; D009285:Naphthoquinones