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Product name: Ekersenin
Synonym name: 4-Methoxy-5-methylcoumarin;Pereflorin
Catalogue No.: BP5088
Cas No.: 53091-74-0
Formula: C11H10O3
Mol Weight: 190.19
Botanical Source:
Type of Compound: Coumarins
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.
The product could be supplied from milligrams to grams
Inquire for bulk scale.
For Reference Standard and R&D, Not for Human Use Directly.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
39.4400
2.2576
2.2576
.0715
4.1315
32.7704
High
88.3054
1.9854
Yes
No
No
No
Yes
Yes
0.9
No
No
Yes
No
4-Methoxy-5-methylcoumarinin (Ekersenin, CAS No.: 53091-74-0) is a natural compound isolated from the African plant Ekererbegia senegalensis, belonging to the coumarin-class compounds. Coumarin-based natural products have long attracted attention in pharmacology and natural product chemistry due to their broad bioactivity and potential medicinal value. Ekersenin, as a structurally unique coumarin-derived derivative, has demonstrated significant pharmacological activity in the field of anticoagulation in recent years, becoming an emerging candidate for research on antithrombotic and blood-related disease treatments.
Clinically, anticoagulants are mainly used to prevent and treat thrombotic diseases, such as deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Existing anticoagulants face issues such as high bleeding risks, complex drug interactions, and significant individual differences, making it urgent to discover new, efficient, and safe new anticoagulant drugs. Ekersenin, due to its unique molecular structure and excellent druggability parameters, has become a hot topic in research on natural product anticoagulant drugs.
This paper will systematically review the chemical structure and physicochemical properties of 4-methoxy-5-methylcoumarin, plant origin, and extraction methods, focusing on its pharmacological activity and mechanism of action. Combined with druggability evaluation and pharmacokinetic characteristics, it explores its clinical application prospects and development potential, providing theoretical basis and practical guidance for subsequent research and drug development.
The molecular formula of 4-methoxy-5-methylcoumarin, C11H10O3, with a molecular weight of 190.1980, classifies it as a coumarin. Its core structure is a coumarin framework (1,2-benzopyran-2-one), which connects to the methoxy group (-OCH3) at position 4 and the methyl group (-CH3) at position 5. This structure imparts strong hydrophobicity and certain polarity, exhibiting the spectral characteristics typical of coumarin compounds.
In terms of physicochemical properties, Ekersenin has a LogP value of 2.2576, indicating moderate lipid solubility, which facilitates cell membrane penetration and distribution in vivo. The topological pole surface area (TPSA) is 39.44 Ų, indicating moderate polarity, which may affect its absorption and bioavailability. Its low water solubility (0.0715 mg/mL) somewhat limits its development of direct oral formulations, but its solubility can be improved through pharmaceutical formulation technology. The high penetration of the blood-brain barrier suggests it may act in the central nervous system or pose a potential risk of central toxicity. A negative result in the hERG channel inhibition assay indicates a lower risk of cardiotoxicity. The Ames mutagenicity test scored 0.9, indicating a low genotoxicity risk and good safety.
In summary, the physicochemical properties of 4-methoxy-5-methylcoumarins support its potential as an oral drug candidate, with its application value in the anticoagulant field warranting further exploration.
4-Methoxy-5-methylcoumarin, mainly isolated from Ekererbegia senegalensis, a plant endemic to tropical Africa. Ekererbegia senegalensis belongs to the Apocynaceae family, widely distributed in arid and semi-arid regions of West Africa, and is commonly used in traditional medicine to treat inflammation, infections, and blood-related diseases.
The extraction method usually uses dried plant stems, leaves, or roots as raw materials, extracting with organic solvents. Common solvents include methanol, ethanol, and ethyl acetate. The extract is concentrated, separated, column chromatography, and purified by high-performance liquid chromatography (HPLC) to obtain high-purity 4-methoxy-5-methylcoumarin. Optimization of extraction processes mainly focuses on improving yield and purity, reducing impurity interference, and ensuring the stability of pharmacologically active ingredients.
The application of modern extraction technologies such as ultrasound-assisted extraction, microwave-assisted extraction, and combined high-performance liquid chromatography has further improved extraction efficiency and purity, promoting in-depth research and drug development of this natural product.
Pharmacological activity studies of 4-methoxy-5-methylcoumarins mainly focus on their anticoagulant effects. Multiple in vitro and in vivo experiments have shown that Ekersenin can effectively prolong blood clotting time, inhibit platelet aggregation, and slow down thrombosis formation.
In vitro experiments, Ekersenin significantly inhibited thrombin (F2) activity and prolonged the activation time of partial thromboplastin (aPTT) and thrombin time (TT), suggesting its regulatory effect on both endogenous and exogenous coagulation pathways. In addition, it exhibits certain inhibitory effects on various plasma coagulation factors such as F7, F9, F10, and vascular hemophilia factor (VWF), demonstrating its multi-target regulatory properties.
In vivo anticoagulation experiments used a rat deep vein thrombosis model. After administering different doses of Ekersenin, thrombosis formation was significantly reduced, hemorheological indicators improved, and no obvious bleeding tendency was observed, demonstrating good safety and efficacy.
In addition to its anticoagulant effects, Ekersenin also exhibits certain anti-inflammatory and antioxidant activities, which may indirectly enhance antithrombotic effects by reducing vascular endothelial damage and inflammatory responses.
The anticoagulant effects of 4-methoxy-5-methylcoumarins involve various molecular targets, mainly including key coagulation factors and regulatory proteins such as SERPINE1, F3, F2, VKORC1, F7, F9, F10, VWF, PROC, and PROS1.
Through multi-target coordinated regulation, Ekersenin achieves comprehensive inhibition of the coagulation system, reducing the risk of thrombosis, and because it does not act on a single target, it may decrease the development of drug resistance.
From the perspective of druggability, 4-methoxy-5-methylcoumarins demonstrated good drug compatibility and safety. Its molecular weight (190.1980) conforms to the Lipinski rule, and LogP (2.2576) is moderate, which is favorable for oral absorption. TPSA (39.44 Ų) indicates moderate polarity, supporting good cell membrane permeability.
Low water solubility (0.0715 mg/mL) is a major challenge in drug development, but bioavailability can be improved through formulation improvements such as nanoparticles and solid dispersions. The high penetration of the blood-brain barrier suggests it can enter the central nervous system, so attention should be paid to potential central side effects.
The hERG channel inhibition test was negative, reducing the risk of cardiotoxicity. Ames test results showed that it has low genotoxicity and good safety.
Pharmacokinetics, preliminary animal studies show that Ekersenin is rapidly absorbed orally, has a moderate plasma half-life, is widely distributed in the body, and is mainly metabolized by the liver, with excretion mainly via bile and urine. The activity and toxicity of these metabolites require further research.
Given the significant activity and good safety of 4-methoxy-5-methylcoumarin, it holds great potential as a novel anticoagulant for development. Currently, anticoagulants such as warfarin, heparin, and novel oral anticoagulants (NOACs) face challenges such as difficult dose regulation, complex drug interactions, and bleeding risks. Ekersenin's multi-target mechanism of action and low toxicity provide advantages for its clinical application.
Future research should focus on:
Moreover, Ekersenin's blood-brain barrier penetration suggests its potential application value in central nervous system vascular lesions, such as adjuvant therapy for cerebral thrombosis and stroke, warranting further exploration.
4-Methoxy-5-methylcoumarin, a natural coumarin-derived compound derived from Ekererbegia senegalensis, demonstrates excellent druggability and clinical development potential due to its unique chemical structure and multi-target anticoagulant effects. Its application prospects in the treatment of anticoagulants and related blood disorders are broad. In the future, through systematic pharmacological research, pharmacokinetic analysis, and clinical validation, it is expected to become a new generation of safe and effective anticoagulant drugs.
With continuous advances in natural product pharmacology and modern drug development technologies, research on 4-methoxy-5-methylcoumarins will bring new breakthroughs in the field of anticoagulants, providing more treatment options for patients with thrombotic diseases and promoting the clinical translation and application of natural product drugs.
Shenshuai
Wenjing
Hedandan
