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Synonym name: Coumarinic anhydride; alpha-Benzopyrone; Cumarin
Catalogue No.: BP0402
Cas No.: 91-64-5
Formula: C9H6O2
Mol Weight: 146.145
Botanical Source: Occurs in woodruff (Galium odorata), Melilotus sp., tonka beans (Coumarouna odorata, preferred genus name Dipteryx) , lavender oil and other plants
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
HPLC of Coumarin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
26.3000
1.3900
1.3900
1700.0000
High
No
No
No
Yes
No
Positive
Coumarin, CAS number 91-64-5, is a class of natural organic compounds widely found in various plants, attracting attention for its unique aroma and diverse bioactivity. As an effective oral anti-inflammatory agent, coumarins not only demonstrate significant anti-inflammatory effects but also possess antibacterial, antifungal, and anticancer activities, demonstrating their significant value in the field of natural product pharmacology. In recent years, with in-depth research into the biological activity and mechanisms of coumarin, its potential in multiple therapies such as anticoagulation, anti-inflammation, and antitumor has gradually been revealed, making it one of the hotspots in drug development and clinical application.
This paper aims to systematically review the chemical structure and physicochemical properties, plant origins, and extraction methods of coumarin, combined with the latest pharmacological activity studies, to deeply explore its mechanism of action and related molecular targets, evaluate its druggability and pharmacokinetic characteristics, and finally look ahead to its clinical application prospects, providing theoretical basis and research directions for natural product pharmacology and new drug development.
The chemical name of coumarins is 1,2-benzo-2-oxo-1-cyclohexelenone, with the molecular formula C9H6O2 and a molecular weight of 146.14. Its structural core is the benzo-α-pyranone ring, which has a typical coumarin backbone. Coumarin's LogP value is 1.39, indicating moderate lipid solubility and facilitating penetration of cell membranes and the blood-brain barrier (BBB has high permeability). Its topological polar surface area (TPSA) is 26.3 Ų, with 2 hydrogen bond acceptors, indicating low polarity that facilitates oral absorption and intracellular distribution.
Coumarin has relatively high water solubility (1700 mg/L), a property that helps with its distribution and metabolism in the body. Toxicological data showed that the half-lethal dose (LD50) of coumarins was 293 mg/kg, suggesting some acute toxicity and hepatotoxicity, but no significant cardiotoxicity or hERG channel inhibition. A positive Ames test suggests a certain genotoxicity risk, so safety should be carefully evaluated during use.
Coumarins are widely found in multiple plant families and genera such as the Apiaceae, Fabaceae, and Lamiaceae families, with particularly high levels in plants like Melilotus officinalis, cinnamon (Cinnamomum spp.), Lithospermum erythrorhizon (Lithospermum erythrorhizon), and licorice (Glycyrrhiza glabra). Coumarins in plants mostly exist in free or bound forms (such as coumarins), giving plants their unique aroma and biological activity.
Traditional methods for extracting coumarins mainly include solvent extraction, distillation, and supercritical fluid extraction. Solvent extraction often uses ethanol, methanol, or ethyl acetate as solvents, combined with ultrasound-assisted extraction technology, which can improve extraction efficiency and purity. Distillation is suitable for volatile extraction of coumarin, especially steam distillation. In recent years, green extraction technologies such as supercritical CO2 extraction have gradually become research hotspots for coumarins due to their efficiency and environmental friendliness.
After extraction, coumarins are usually purified by column chromatography, recrystallization, and other methods to obtain high-purity compounds for pharmacological research and formulation development.
As an effective oral anti-inflammatory agent, coumarin's anti-inflammatory effects mainly lie in inhibiting the release of inflammatory mediators and regulating inflammatory signaling pathways. Multiple in vivo and in vitro experiments have shown that coumarins can significantly reduce the expression of inflammatory factors such as TNF-α, IL-1β, and IL-6, thereby alleviating tissue inflammatory responses. Additionally, coumarins exert anti-inflammatory effects by inhibiting the NF-κB signaling pathway and the MAPK pathway, reducing the activation and infiltration of inflammatory cells.
Coumarins exhibit inhibitory effects on various bacteria and fungi. In vitro experiments have shown that coumarin has certain antibacterial activity against both Gram-positive bacteria (such as Staphylococcus aureus) and Gram-negative bacteria (such as Escherichia coli). Its antifungal effect mainly targets common pathogenic fungi such as Candida albicans, possibly achieved by disrupting cell membrane structure and inhibiting key enzyme activity.
In recent years, the anti-cancer potential of coumarins has attracted widespread attention. Research has found that coumarins can inhibit tumor growth through multiple mechanisms, including inducing tumor cell apoptosis, blocking the cell cycle, and inhibiting tumor angiogenesis and metastasis. Coumarin exhibits cytotoxic effects on various tumor cell lines including breast, lung, and colon cancer. Its anticancer activity is closely related to its regulation of multiple signaling pathways (such as PI3K/Akt, Wnt/β-catenin).
Coumarin, as an anticoagulant, has a long history of research, especially its derivative warfarin, which is widely used in clinical anticoagulant therapy. Coumarins themselves exert anticoagulant effects by regulating the activity of coagulation factors and related proteins. Its targets include key coagulation factors and regulatory proteins such as SERPINE1, F3, F2, VKORC1, F7, F9, F10, VWF, PROC, and PROS1, which can effectively prolong clotting time and prevent thrombosis.
The multiple pharmacological activities of coumarin stem from its ability to regulate various molecular targets. Its anti-inflammatory mechanism mainly inhibits NF-κB and MAPK signaling pathways, reducing the expression of pro-inflammatory cytokines and enzymes. Antibacterial and antifungal effects may involve cell membrane destruction and inhibition of key metabolic enzymes.
In terms of anticancer treatment, coumarins inhibit tumor cell growth and induce apoptosis by regulating apoptosis-related proteins (such as Bcl-2, Caspase family), cell cycle regulatory factors (such as Cyclin D1), and signaling pathways (PI3K/Akt, Wnt/β-catenin).
In terms of anticoagulant effects, coumarins inhibit the activity of vitamin K epoxyreductase (VKORC1), block the γ-carboxylation of vitamin K-dependent coagulation factors (F7, F9, F10, F2), reduce the activity of clotting factors, and achieve anticoagulant effects. Additionally, coumarins regulate the functions of plasma anticoagulant proteins (such as PROC and PROS1) and platelet-associated proteins (VWF), comprehensively controlling the blood coagulation process.
Coumarin's molecular weight was 146.14, LogP value 1.39, TPSA 26.3, meeting the Lipinski rule, and demonstrating good oral bioavailability and cell membrane permeability. Its high water solubility benefits its distribution in the body, but it may also affect its intestinal absorption efficiency. Coumarin can effectively cross the blood-brain barrier, suggesting its potential application in the treatment of central nervous system diseases.
Toxicological evaluations indicate that coumarin carries certain hepatotoxicity risks and that liver safety should be prioritized in drug development. Its LD50 is 293 mg/kg, indicating moderate acute toxicity. Coumarin showed no significant cardiotoxicity or hERG channel inhibition, reducing the risk of adverse cardiac reactions. However, a positive Ames test suggests possible genotoxicity, and further evaluation of its long-term safety is needed.
Pharmacokinetics, coumarins are metabolized in the body mainly through hepatic hydroxylation, producing metabolites such as hydroxycoumarin. Its metabolic process may involve the cytochrome P450 enzyme system, posing potential risks of drug interactions. Coumarin's half-life is moderate and suitable for oral administration, but its formulation needs to be optimized to improve bioavailability and safety.
Coumarin, as a versatile natural product, possesses broad pharmacological activity and potential clinical applications. Its anti-inflammatory, antibacterial, antifungal, and anticancer effects provide new ideas and candidate drug foundations for the treatment of various diseases. Especially in the field of anticoagulants, coumarins and their derivatives have become important drugs in clinical anticoagulant therapy. In the future, through structural modification and dosage form innovation, safer and more effective new anticoagulants are expected to be developed.
However, issues with coumarin's hepatotoxicity and genotoxicity limit its widespread direct use as a drug. Future research should focus on its toxicological mechanisms, optimize its structure to reduce toxicity, and strengthen research on its pharmacokinetic properties to enhance its clinical safety and efficacy.
Additionally, based on the structural diversity of coumarin, developing new derivatives and combination formulations combined with modern drug delivery systems is expected to expand its applications in oncology, infections, and inflammatory diseases. In-depth analysis of multi-target mechanisms will also facilitate the formulation of precision therapeutic strategies for coumarin-related drugs.
As a natural product with rich biological activity, coumarin demonstrates broad application potential in anti-inflammatory, antibacterial, antifungal, cancer, and anticoagulant properties. Its unique chemical structure and excellent physicochemical properties provide a solid foundation for drug development. Despite certain toxicological risks, coumarins remain an important subject for natural product pharmacological research and new drug development.
In the future, through multidisciplinary collaboration and combining modern medicinal chemistry, molecular biology, and pharmacological technologies, the mechanism of coumarin's action and safety optimization will be deeply explored, which is expected to promote its widespread clinical application and benefit more patients. Research on coumarins not only enriches the theoretical framework of natural product pharmacology but also provides valuable examples and insights for natural drug innovation.
Shenshuai
Wenjing
Hedandan
