Coumarins: Bioactivity, Synthesis and Labelling

**91**

**1. Introduction**

**Chapter 5**

Derivatives

*Robbert Bipat*

**Abstract**

From Rat Poison to Medicine:

Medical Applications of Coumarin

Historical reports mention the application of medicinal plants containing coumarins against various ailments. Current research suggests that at least some of the actions described may be attributable to the action of these coumarins. Warfarin and its derivatives are coumarins used today in medical practice. Their mechanism of action lies in the competitive antagonism of vitamin K, through which they inhibit coagulation in the body by preventing the production of prothrombin. Due to this action, these coumarins are a major group of drugs with anticoagulant activity. Anticoagulants reduce the risks of undesirable blood clots leading to myocardial infarction, pulmonary embolism, and ischemic stroke among others. The anticoagulant activity can also lead to undesired bleeding. Extreme caution is warranted when given to menstruating women, patients suffering from disorders prone to bleeding like gastric ulcer and rheumatoid arthritis, and to persons with a high likelihood of blunt and sharp trauma. In addition, there is a significant augmentation of the anticoagulant activity when used in combination with non-steroidal antiinflammatory agents and agents interfering with the metabolism of the coumarins. Recent findings propose additional uses like anti-tumor and antibiotic actions for coumarins. The clinical application of these actions has yet to be demonstrated.

**Keywords:** warfarin, coumarin, anticoagulant, prothrombin, coagulation cascade,

Coumarins are members of the benzopyrone class of organic compounds that are found in many plants [1] and possess a variety of pharmacological properties such as antimicrobial, anti-inflammatory, antidiabetic, and antioxidant activity, as well as a significant influence on physiological processes like enzyme inhibitory activity [2]. Despite the wide availability of coumarins and their lead compounds and metabolites in natural products [3], their application up till now has been mostly limited to the anticoagulant activity of warfarin derived from dicoumarol and its analogues [4]. The mechanism of action of these anticoagulants lies in the competitive antagonism of vitamin K, through which they inhibit coagulation of blood in the body by preventing the production of prothrombin and several other coagulation factors [5]. Due to this action, these coumarins are a major group of oral drugs with anticoagulant activity. Anticoagulants reduce the risks of undesirable

adverse reaction, rodenticide, embryopathy, vitamin K
