Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Coumarins as Potential Anticoagulant Agents


Affiliations
1 Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS) 1Department of Pharmaceutical Chemistry, Mangalore,, India
2 Manipal Academy of Higher Education, Manipal College of Pharmaceutical Sciences (MCOPS) 2Department of Pharmaceutical Chemistry, Manipal,, India
     

   Subscribe/Renew Journal


Major classes of plant metabolites that display a diversity of bioactivities are the Coumarin derivatives. At present, majority of the clinical anti-coagulant agents are coumarins, namely dicoumarol, acenocoumarol and warfarin. The victims who consume coumarins are antidotes should be kept under observation for unfavorable reaction. Phenprocoumon and warfarin, the Vitamin K adversaries, are the front-line oral anti-coagulants for prime and peripheral inhibition of cerebral embolism in victims with atrial fibrillation. Vitamin K adversaries have the capacity of reducing the risk of stroke exceptionally, but their usage is curbed due to some major disadvantages, such as the risk of intracranial and gastrointestinal bleeding, the requirement for systematic laboratory tests for therapy adjustment, interactions with a number of drugs and nutrients, and narrow therapeutic window. At present, latest oral anti-coagulants, namely direct factor Xa inhibitors (e.g., apixaban, rivaroxaban) and direct thrombin inhibitors (e.g., dabigatran), are evolved and tried out in clinical experiments. For the inhibition of cerebral embolism in victims with atrial fibrillation, Rivaroxaban and Dabigatran are currently validated. The role of blood clotting in challenging areas such as the therapeutic potentials of influence over coagulation and the pathogenesis of illness of uncertain etiology shows its biologic and pathologic importance. With growing tempo, acquiring from numerous disciplines – physical, biochemical, physiologic, biochemical, pathologic and clinical, progression has happened swiftly. Adequate proficiency has become handy for over 2 decades in order to grant comprehensive therapeutic requisition. Extensive usage of anti-coagulants and the possibility of their augmentation as vascular and thrombo-embolic sickness have been becoming important as serious medical problems, thereby making re-examination of ample guiding essentials needful.

Keywords

Coumarin, Anti-coagulant, Vitamin K, Blood clotting, Coagulation.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Thomas R. Hari R. Joy J. Krishnan S. Swathy AN. Nair SS. Manakadan AA et al In silico Docking Approach of Coumarin Derivatives as an Aromatase Antagonist. Research Journal of Pharmacy and Technology. 2015; 8(12):1673-78. DOI:10.5958/0974-360X.2015.00302.9
  • Sandeep G. Ranganath YS. Bhasker S. Rajkumar N. Synthesis and Biological Screening of Some Novel Coumarin Derivatives. Asian J Research Chem. 2009; 2(1):46-48.
  • Monika N. Verma R. Sharma SK. Synthetic Study of Vitamin K3 (Menadione, 2-methyl-1, 4-naphthoquinone): A Review. Asian J Research Chem. 2012; 5(9):1200-04.
  • Jainab NH. Sivachidambaram P. Yuvaraju J. Beyatricks J. Raj B Microwave Mediated Synthesis, Characterisation and Biological activity of Certain New Mannich Bases of Isatin and Coumarin. Asian J Research Chem. 2014; 7(2):176-81.
  • Braun AE. Gonzalez AG. Coumarins. Natural Product Reports. 1997; 5:433–558. https://doi.org/10.1039/NP9971400465
  • Murray RDH. Coumarins. Nat Prod Rep. 1995; 5:445–554.
  • Xu J. Kjer J. Sendker J. Wray V. Guan H. Edrada R. Muller WEG et al Cytosporones, coumarins, and an alkaloid from the endophytic fungus Pestalotiopsis sp. isolated from the Chinese mangrove plant Rhizophoramucronata. Bioorganic and Medicinal Chemistry. 2009; 17:7362–67. https://doi.org/10.1016/j.bmc.2009.08.031
  • Yang XL. Awakawa T. Wakimolo T. Abe I. Induced production of novel prenyldepside and coumarins in endophytic fungi Pestalotiopsis acacia. Tetrahedron Letters. 2013; 54:5814–17. DOI: 10.1016/j.tetlet.2013.08.054
  • Biswas B. Sen PK. Venkateswaran RV. Bargellini condensation of coumarins. Expeditious route to o-carboxyvinylphenoxyisobutyric acids and application to the synthesis of sesquiterpeneshelianane, heliannuol A and heliannuol.Tetrahedron. 2007; 63(48):12026–36. DOI: 10.1016/j.tet.2007.09.006
  • Khan AT. Das DK. Islam K. Das P. A simple and expedient synthesis of functionalized pyrido [2, 3-c] coumarin derivatives using molecular iodine catalyzed three-component reaction. Tetrahedron Letters. 2012; 53:6418–22. https://doi.org/10.1016/j.tetlet.2012.09.051
  • Schofield FW. A brief account of a disease in cattle simulating hemorrhagic septicemia due to feeding sweet clover. Canadian Journal of Veterinary Research. 1984; 25(12):453-5.
  • Roderick LM. The pathology of sweet clover disease in cattle. Journal of the American Veterinary Medical Association. 1929; 74:314-25.
  • Momin KI. Suryawanshi VB. Bondge AS. Dawale JK. Synthesis and biological evaluation of coumarin acetamide derivatives. Asian J Research Chem 2018; 11(2):453-58. http://dx.doi.org/10.5958/0974-4150.2018.00082.2
  • Arora P. Ranawat MS. Arora N. Synthesis and Screening of Some Novel Coumarin Derivatives for Antipsychotic Activity. Research J Pharm and Tech. 2012; 5(7):968-72.
  • Campbell HA. Link KP. Studies on the hemorrhagic sweet clover disease. IV. The isolation and crystallization of the hemorrhagic agent. Nutrition Reviews. 2009; 32(8):244-46.
  • Thomas R. Hari R. Joy J. Krishnan S. Swathy AN. Nair SS. Manakadan AA et al In silico Docking Approach of Coumarin Derivatives as an Aromatase Antagonist. Research J Pharm and Tech. 2015; 8(12):1673-78. http://dx.doi.org/10.5958/0974-360X.2015.00302.9
  • Kumar A. Shetty P. Amrutha CL. Vaz DR. Baby A. Synthesis and Antimicrobial Evaluation of Some Novel Derivatives of Coumarin Moiety. Research J Pharm and Tech. 2016; 9(5):545-48. https://doi.org/10.5958/0974-360X.2016.00103.7
  • Bingham JB. Meyer OO. Pohle FJ. Studies on the hemorrhagic agent 3,3’-methyl-enebis (4-hydroxycoumarin). I. Its effect on the prothrombin and coagulation time of the blood of dogs and humans. American Journal of the Medical Sciences. 1941; 202:563-78.
  • Butt HR. Allen EU. Bollman JL. A preparation from spoiled sweet clover 3,3’-methyl-enebis (4-hydroxycoumarin) which prolongs coagulation and prothrombin time of blood:preliminary report of experiments and clinical studies. Proceedings of the Staff Meeting Mayo Clin. 1941; 16:388-95.
  • Nair NP. Allen EU. Bollman JL. In-silico Docking Studies of Coumarin Derivatives as Caspase 8 and PDE4 Antagonist. Research J Pharm and Tech. 2016; 9(12):2199-2204. https://doi.org/10.5958/0974-360X.2016.00445.5
  • Kumar A. Kumar P. Pinto JS. Bhashini. Akshata. Synthesis and Antimicrobial Evaluation of Some new Coumarinyl Schiff Base Derivatives. Research J Pharm and Tech. 2018; 11(11):4946-48. http://dx.doi.org/10.5958/0974-360X.2018.00900.9
  • Li T. Chang CY. Jin DY. Lin PJ. Khvorova A. Stafford DW Identification of the gene for vitamin K epoxide reductase. Nature. 2004; 427:541–44. https://doi.org/10.1038/nature02254
  • Naasani N. Harbali J. Kandil F. Synthesis and Biological Evaluation of 3-thiosemicarbazoneacetyl Coumarin derivatives as Antioxidant. Research J Pharm and Tech. 2020; 13(10):4565-69. https://doi.org/10.5958/0974-360X.2020.00804.5
  • Debasish S. Tripti S. Molecular Docking studies of 3-substituted 4-phenylamino coumarin derivatives as Chemokine receptor inhibitor. Research J Pharm and Tech. 2021; 14(2):943-48. https://doi.org/10.5958/0974-360X.2021.00168.2
  • Panneerselvam S. Baglin C. Lefort W. Baglin T. Analysis of risk factors for over-anticoagulation in patients receiving long-term warfarin. British Journal of Haematology. 1998; 103:422–24. https://doi.org/10.1046/j.1365-2141.1998.00988.x
  • Kavitha K. Sree BK. Preethi JP. Kumar PK. Rajvel R. Sivakumar T. Synthesis, Characterization and Biological Activity of Coumarin Derivatives. Research J Science and Tech. 2012; 4(6):252-57.
  • Lubetsky A. Dekel-Stern E. Chetrit A. Lubin F. Haklin H. Vitamin K intake and sensitivity to warfarin in patients consuming regular diets. Thrombosis and Haemostasis. 1999; 81(3):396–99.
  • Link KP. The discovery of Dicumarol and its sequels. Circulation. 1959; XIX:97-107. https://doi.org/10.1161/01.cir.19.1.97
  • Holmes RW. Love J. Suicide attempt with warfarin, a bis-hydroxycoumarin-like rodenticide. Journal of the American Medical Association. 1952; 148(11):935-37. doi:10.1001/jama.1952.62930110003013a
  • Weiner M. Pharmacologic considerations of antithrombotic therapy. Advances in Pharmacol and Pharmacy. 1962; 1:277-307. https://doi.org/10.1016/S1054-3589(08)60511-6
  • Garner RJ. A spectroscopic study of the fate of warfarin and coumachlor in the rat. Nordisk Veterinary Medicine. 1957; 9:464.

Abstract Views: 157

PDF Views: 0




  • Coumarins as Potential Anticoagulant Agents

Abstract Views: 157  |  PDF Views: 0

Authors

Abhishek Kumar
Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS) 1Department of Pharmaceutical Chemistry, Mangalore,, India
Pankaj Kumar
Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS) 1Department of Pharmaceutical Chemistry, Mangalore,, India
Shravya H
Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS) 1Department of Pharmaceutical Chemistry, Mangalore,, India
Aravind Pai
Manipal Academy of Higher Education, Manipal College of Pharmaceutical Sciences (MCOPS) 2Department of Pharmaceutical Chemistry, Manipal,, India

Abstract


Major classes of plant metabolites that display a diversity of bioactivities are the Coumarin derivatives. At present, majority of the clinical anti-coagulant agents are coumarins, namely dicoumarol, acenocoumarol and warfarin. The victims who consume coumarins are antidotes should be kept under observation for unfavorable reaction. Phenprocoumon and warfarin, the Vitamin K adversaries, are the front-line oral anti-coagulants for prime and peripheral inhibition of cerebral embolism in victims with atrial fibrillation. Vitamin K adversaries have the capacity of reducing the risk of stroke exceptionally, but their usage is curbed due to some major disadvantages, such as the risk of intracranial and gastrointestinal bleeding, the requirement for systematic laboratory tests for therapy adjustment, interactions with a number of drugs and nutrients, and narrow therapeutic window. At present, latest oral anti-coagulants, namely direct factor Xa inhibitors (e.g., apixaban, rivaroxaban) and direct thrombin inhibitors (e.g., dabigatran), are evolved and tried out in clinical experiments. For the inhibition of cerebral embolism in victims with atrial fibrillation, Rivaroxaban and Dabigatran are currently validated. The role of blood clotting in challenging areas such as the therapeutic potentials of influence over coagulation and the pathogenesis of illness of uncertain etiology shows its biologic and pathologic importance. With growing tempo, acquiring from numerous disciplines – physical, biochemical, physiologic, biochemical, pathologic and clinical, progression has happened swiftly. Adequate proficiency has become handy for over 2 decades in order to grant comprehensive therapeutic requisition. Extensive usage of anti-coagulants and the possibility of their augmentation as vascular and thrombo-embolic sickness have been becoming important as serious medical problems, thereby making re-examination of ample guiding essentials needful.

Keywords


Coumarin, Anti-coagulant, Vitamin K, Blood clotting, Coagulation.

References