dicoumarol

Dicoumarol is a naturally occurring anticoagulant and a derivative of coumarin. It was first identified in the 1940s as the substance in moldy sweet clover hay responsible for a hemorrhagic disease in cattle, a discovery that eventually led to the development of warfarin. Mechanistically, dicoumarol acts as a vitamin K antagonist by inhibiting the enzyme **vitamin K epoxide reductase (VKORC1)**. This inhibition prevents the recycling of vitamin K, which is a necessary cofactor for the gamma-carboxylation of glutamate residues on clotting factors II (prothrombin), VII, IX, and X, as well as proteins C and S. Without this modification, these factors cannot bind calcium or phospholipid membranes, rendering them inactive. Clinically, dicoumarol was used for the prophylaxis and treatment of venous thrombosis and pulmonary embolism, but it has been largely superseded by warfarin due to its slower onset of action and unpredictable gastrointestinal absorption. Additionally, dicoumarol is a potent inhibitor of **NAD(P)H:quinone oxidoreductase 1 (NQO1)**, a property frequently exploited in biochemical research to study oxidative stress and cancer cell metabolism.

Brand names

DicumarolMelitoxin

Other names

DicumarolBishydroxycoumarin3,3'-methylenebis(4-hydroxycoumarin)