Osthenol
(Synonyms: 7-羟基-8-(3-甲基-2-丁烯)-二氢苯并吡喃,Ostenol) 目录号 : GC61162
Osthenol(Ostenol)是从独活干根中分离得到的一种前酰化香豆素，是一种可逆的，选择性的竞争性人单胺氧化酶-A(hMAO-A)抑制剂(Ki=0.26µM)。Osthenol对重组hMAO-A具有潜在的选择性抑制作用，IC50为0.74µM，对hMAO-A和hMAO-B表现出较高的选择性指数。
Cas No.:484-14-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Osthenol (Ostenol), a prenylated coumarin isolated from the dried roots of Angelica pubescens, is selective, reversible, and competitive human monoamine oxidase-A (hMAO-A) inhibitor (Ki=0.26 µM). Osthenol potently inhibits recombinant hMAO-A with an IC50 of 0.74 µM and shows a high selectivity index for hMAO-A versus hMAO-B[1].
[1]. Baek SC, et al. Osthenol, a prenylated coumarin, as a monoamine oxidase A inhibitor with high selectivity. Bioorg Med Chem Lett. 2019;29(6):839-843. [2]. Liao ZC, et al. Zhongguo Zhong Yao Za Zhi. 2017;42(15):2999-3003.
| Cas No. | 484-14-0 | SDF | |
| 别名 | 7-羟基-8-(3-甲基-2-丁烯)-二氢苯并吡喃,Ostenol | ||
| Canonical SMILES | O=C1C=CC2=CC=C(O)C(C/C=C(C)\C)=C2O1 | ||
| 分子式 | C14H14O3 | 分子量 | 230.26 |
| 溶解度 | DMSO : 100 mg/mL (434.29 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.3429 mL | 21.7146 mL | 43.4292 mL |
| 5 mM | 0.8686 mL | 4.3429 mL | 8.6858 mL |
| 10 mM | 0.4343 mL | 2.1715 mL | 4.3429 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Characterization of Osthenol metabolism in vivo and its pharmacokinetics
Xenobiotica 2020 Jul;50(7):839-846.PMID:31847686DOI:10.1080/00498254.2019.1705427.
Osthenol, a prenylated coumarin, is a C8-prenylated derivative of umbelliferone isolated from the root of Angelica koreana and Angelica dahurica, an intermediate and is known as a major metabolite of desmethyl-osthole.The various pharmacological effects of Osthenol have been reported. In previous studies, we investigated five hydroxylated metabolites by cytochromes P450 (CYP) and glucuronide conjugates of Osthenol by uridine diphosphate-glucuronosyltransferases (UGTs). However, Osthenol have very few studies have been reported on its pharmacokinetic (PK) profiling, we reported the PK parameters in mouse of Osthenol through this study.After oral (5 and 20 mg/kg) and intravenous (5 mg/kg) administration, the concentration of Osthenol in plasma was determined by LC-MS/MS. The quantitative method was validated in terms of linearity, accuracy, and precision. When 5 and 20 mg/kg of Osthenol were orally administered, the bioavailability (BA) was found to be very low at 0.43 and 0.02%, respectively.In fact, Osthenol was mostly metabolized to a two-Phase II conjugates, a sulfonyl and glucuronyl-osthenol, in the blood, which was determined by LC-HR/MS analysis of the blood sample. Because Osthenol is rapidly metabolized to two conjugates by first-pass effect the BA of Osthenol is low after oral administration.
Osthenol, a prenylated coumarin, as a monoamine oxidase A inhibitor with high selectivity
Bioorg Med Chem Lett 2019 Mar 15;29(6):839-843.PMID:30686752DOI:10.1016/j.bmcl.2019.01.016.
Osthenol (6), a prenylated coumarin isolated from the dried roots of Angelica pubescens, potently and selectively inhibited recombinant human monoamine oxidase-A (hMAO-A) with an IC50 value of 0.74 µM and showed a high selectivity index (SI > 81.1) for hMAO-A versus hMAO-B. Compound 6 was a reversible competitive hMAO-A inhibitor (Ki = 0.26 µM) with a potency greater than toloxatone (IC50 = 0.93 µM), a marketed drug. Isopsoralen (3) and bakuchicin (1), furanocoumarin derivatives isolated from Psoralea corylifolia L., showed slightly higher IC50 values (0.88 and 1.78 µM, respectively) for hMAO-A than 6, but had low SI values (3.1 for both). Other coumarins tested did not effectively inhibit hMAO-A or hMAO-B. A structural comparison suggested that the 8-(3,3-dimethylallyl) group of 6 increased its inhibitory activity against hMAO-A compared with the 6-methoxy group of scopoletin (4). Molecular docking simulations revealed that the binding affinity of 6 for hMAO-A (-8.5 kcal/mol) was greater than that for hMAO-B (-5.6 kcal/mol) and that of 4 for hMAO-A (-7.3 kcal/mol). Docking simulations also implied that 6 interacted with hMAO-A at Phe208 and with hMAO-B at Ile199 by carbon hydrogen bondings. Our findings suggest that Osthenol, derived from natural products, is a selective and potent reversible inhibitor of MAO-A, and can be regarded a potential lead compound for the design of novel reversible MAO-A inhibitors.
Characterization of CYPs and UGTs Involved in Human Liver Microsomal Metabolism of Osthenol
Pharmaceutics 2018 Aug 30;10(3):141.PMID:30200214DOI:10.3390/pharmaceutics10030141.
Osthenol is a prenylated coumarin isolated from the root of Angelica koreana and Angelica dahurica, and is an O-demethylated metabolite of osthole in vivo. Its various pharmacological effects have been reported previously. The metabolic pathway of Osthenol was partially confirmed in rat osthole studies, and 11 metabolic products were identified in rat urine. However, the metabolic pathway of Osthenol in human liver microsomes (HLM) has not been reported. In this study, we elucidated the structure of generated metabolites using a high-resolution quadrupole-orbitrap mass spectrometer (HR-MS/MS) and characterized the major human cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT) isozymes involved in Osthenol metabolism in human liver microsomes (HLMs). We identified seven metabolites (M1-M7) in HLMs after incubation in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) and uridine 5'-diphosphoglucuronic acid (UDPGA). As a result, we demonstrated that Osthenol is metabolized to five mono-hydroxyl metabolites (M1-M5) by CYP2D6, 1A2, and 3A4, respectively, a 7-O-glucuronide conjugate (M6) by UGT1A9, and a hydroxyl-glucuronide (M7) from M5 by UGT1A3 in HLMs. We also found that glucuronidation is the dominant metabolic pathway of Osthenol in HLMs.
Isolation and identification of metabolites of osthole in rats
Xenobiotica 2012 Nov;42(11):1120-7.PMID:22630788DOI:10.3109/00498254.2012.689887.
Osthole (Ost), one of the major components of Cnidium monnieri (L.) Cusson, is had the structure of an isopentenoxy-coumarin with a range of pharmacological activities. In the present study, the metabolism of Ost in male Sprague-Dawley rats was investigated by identifying Ost metabolites excreted in rat urine. Following an oral dose of 40 mg/kg Ost, 10 phase I and 3 phase II metabolites were isolated from the urine of rats, and their structures identified on the basis of a range of spectroscopic data, including 2D-NMR techniques. These metabolites were fully characterized as 5'-hydroxyl-osthole (M-1), Osthenol (M-2), 4'-hydroxyl-osthole (M-3), 3, 5'-dihydroxyl-osthole (M-4), 5'-hydroxyl-osthenol (M-5), 4'-hydroxyl-2', 3'-dihydro-osthenol (M-6), 4'-hydroxyl-osthenol (M-7), 3, 4'-dihydroxyl-osthole (M-8), 2', 3'-dihydroxyl-osthole (M-9), 5'-hydroxyl-2', 3'-dihydroosthole (M-10), osthenol-7-O-β-D-glucuronide (M-11), osthole-4'-O-β-D-glucuronide (M-12) and osthole-5'-O-β-D-glycuronate (M-13). This is the first identification of M-1, M-3 to M-13 in vivo. On the basis of the metabolites profile, a possible metabolic pathway for Ost metabolism in rats has been proposed. This is the first systematic study on the phases I and II metabolites of 8-isopentenoxy-coumarin derivative.
Antibacterial activity of coumarins
Z Naturforsch C J Biosci 2005 Sep-Oct;60(9-10):693-700.PMID:16320610DOI:10.1515/znc-2005-9-1006.
The antibacterial activity of coumarin per se and other 45 coumarin derivatives was tested against strains of Bacillus cereus MIP 96016, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus ATCC 25923. The inhibitory effects of coumarins were affected by their substitution patterns. Osthenol (44) showed the most effective antibacterial activity against Gram-positive bacteria with MIC values ranging between 125 and 62.5 microg/ml. These results suggested that the prenyl chain of 44 at position 8 and the presence of OH at position 7 of the benzenic ring are required for the antibacterial activity against these strains.