warfarin has been researched along with lapachol* in 1 studies
1 other study(ies) available for warfarin and lapachol
Article | Year |
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Lapachol inhibition of vitamin K epoxide reductase and vitamin K quinone reductase.
Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] has been shown to be a potent inhibitor of both vitamin K epoxide reductase and the dithiothreitol-dependent vitamin K quinone reductase of rat liver microsomes in vitro. These observations explain the anticoagulant activity of lapachol previously observed in both rats and humans. Lapachol inhibition of the vitamin K epoxide and quinone reductases resembled coumarin anticoagulant inhibition, and was observed in normal strain but not in warfarin-resistant strain rat liver microsomes. This similarity of action suggests that the lactone functionality of the coumarins is not critical for their activity. The initial-velocity steady-state inhibition patterns for lapachol inhibition of the solubilized vitamin K epoxide reductase were consistent with tight binding of lapachol to the oxidized form of the enzyme, and somewhat lower affinity for the reduced form. It is proposed that lapachol assumes a 4-enol tautomeric structure similar to that of the 4-hydroxy coumarins. These structures are analogs of the postulated hydroxyvitamin K enolate intermediate bound to the oxidized form of the enzyme in the chemical reaction mechanism of vitamin K epoxide reductase, thus explaining their high affinity. Topics: Animals; Anticoagulants; Dithiothreitol; Drug Resistance; Kinetics; Microsomes, Liver; Mixed Function Oxygenases; NADH, NADPH Oxidoreductases; Naphthoquinones; Oxidation-Reduction; Quinone Reductases; Rats; Vitamin K Epoxide Reductases; Warfarin | 1984 |