Anticoagulant activity of a naphthoquinone analog of vitamin K and an inhibitor of coenzyme Q10- enzyme systems.

Synthetic 2-hydroxy-3-h-dodecylmercapto-1,4-naphthoquinone is an analog of both vitamin K1 and coenzyme Q10. This naphthoquinone analog is an effective inhibitor of coenzyme Q10-enzymes of mammalian mitochondria, which are components of electron transfer mechanisms of respiration and coupled oxidative phosphorylation. This analog increased the prothrombin time in rats when it was administered orally or parenterally. Vitamin K1 reversed the prothrombin time increase, but that form of coenzyme Q, hexahydrocoenzyme Q4, which has the same phytyl side chain as vitamin K1, did not reverse the increase, constituting the biological differentiation between vitamin K and coenzyem Q. Two benzoquinone analogs of coenzyme Q10, 5-n-octadecylmercapto-2,3-dimethoxy-1,4-benzoquinone and 5-beta-naphthylmercapto-2,3-dimethoxy-1,4-benzoquinone, the latter being a strong inhibitor of coenzyme Q10-enzymes, did not increase the prothrombin time under comparable conditions.