Febrifugine
(Synonyms: 常山乙素) 目录号 : GC38614
A quinazolinone with antimalarial activity
Cas No.:24159-07-7
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
Febrifugine is a quinazolinone alkaloid originally isolated from D. febrifuga that has antimalarial activity.1,2 It reduces parasitemia and decreases mortality in mice infected with the P. berghei strain NK65 when administered at a dose of 1 mg/kg per day beginning prior to or on the day of infection.3
1.Koepfli, J.B., Mead, J.F., and Brockman, J.A., Jr.An alkaloid with high antimalarial activity from Dichroa febrifugaJ. Am. Chem. Soc.69(7)1837(1947) 2.McLaughlin, N.P., Evans, P., and Pines, M.The chemistry and biology of febrifugine and halofuginoneBioorg. Med. Chem.22(7)1993-2004(2014) 3.Murata, K., Takano, F., Fushiya, S., et al.Potentiation by febrifugine of host defense in mice against Plasmodium berghei NK65Biochem. Pharmacol.58(10)1593-1601(1999)
| Cas No. | 24159-07-7 | SDF | |
| 别名 | 常山乙素 | ||
| Canonical SMILES | O=C1N(CC(C[C@H]2NCCC[C@@H]2O)=O)C=NC3=C1C=CC=C3 | ||
| 分子式 | C16H19N3O3 | 分子量 | 301.34 |
| 溶解度 | DMF: 1.5 mg/ml,DMSO: 3.0 mg/ml,Ethanol: 0.1 mg/ml,PBS (pH 7.2): 2.5 mg/ml | 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 | 3.3185 mL | 16.5926 mL | 33.1851 mL |
| 5 mM | 0.6637 mL | 3.3185 mL | 6.637 mL |
| 10 mM | 0.3319 mL | 1.6593 mL | 3.3185 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。
Chemical synthesis of Febrifugine and analogues
Bioorg Med Chem 2018 May 15;26(9):2199-2220.PMID:29681487DOI:10.1016/j.bmc.2018.04.027.
The quinazolinone-containing 2,3-disubstituted piperidines Febrifugine and isofebrifugine have been the subject of significant research efforts since their occurrence in Dichroa febrifuga and their anti-malarial actions were first described in the late 1940s. Subsequently they have also been shown to be present in other plants belonging to the hydrangea family and various analogues of Febrifugine have been prepared in attempts to tune biological properties. The most notable analogue is termed halofuginone and a substantial body of work now demonstrates that this compound possesses potent human disease relevant activities. This review focuses on the literature associated with efforts dedicated towards uncovering the structures of Febrifugine and isofebrifugine, the development of practical methods for their synthesis and the syntheses of structural analogues.
In vitro effects of Febrifugine on Schistosoma mansoni adult worms
Trop Med Health 2020 Jun 4;48:42.PMID:32518498DOI:10.1186/s41182-020-00230-x.
Background: Reports on the antischistosomal effect of several antimalarial drugs such as artesunate, mefloquine, and amodiaquine suggest that Febrifugine, which exerts an antimalarial effect, can also be expected to possess antischistosomal potential. The present study investigates the antischistosomal effects of Febrifugine. Methods: In experiment 1, Schistosoma mansoni adult worm pairs were incubated in a medium alone as a control or supplemented with Febrifugine at 0.05, 0.1, 0.2, and 0.5 μg/ml for 14 days. The morphology of the worms and the egg production of the female worms were observed simultaneously. In experiment 2, the incubation was conducted as in experiment 1, except that the Febrifugine concentrations were reduced to 0.005, 0.01, and 0.02 μg/ml. In addition, S. mansoni adult worms were incubated with either 0.5 μg/ml Febrifugine or none as a control for 5 days and stained with neutral red dye. Results: Febrifugine significantly reduced the survival of S. mansoni male and female worms at concentrations of 0.02-0.5 μg/ml following incubation for 14 days and remarkably inhibited the daily egg output of the female worms. The non-treated male and female worms remained morphologically normal within the period of 14 days, whereas male and female worms treated with Febrifugine at different concentrations gradually twisted and subsequently died. In addition, S. mansoni adult worms were incubated with either 0.5 μg/ml Febrifugine or none as a control for 5 days and stained with neutral red dye. Non-treated male worms were morphologically normal and stained dark red with neutral red, while febrifugine-treated male worms appeared similar to those in the control group and were stained at a slightly lower level of dark red than the non-treated male worms. Non-treated female worms were morphologically normal, and their intestinal tract and vitellaria were stained deep red and dark red, respectively. In contrast, febrifugine-treated female worms were morphologically damaged, and their intestinal tract and vitellaria remained mostly unstained and stained dark red, respectively. Conclusion: Febrifugine exerts potent antischistosomal effects and can be expected to contribute to the development of a novel antischistosomal drug.
The chemistry and biology of Febrifugine and halofuginone
Bioorg Med Chem 2014 Apr 1;22(7):1993-2004.PMID:24650700DOI:10.1016/j.bmc.2014.02.040.
The trans-2,3-disubstituted piperidine, quinazolinone-containing natural product Febrifugine (also known as dichroine B) and its synthetic analogue, halofuginone, possess antimalarial activity. More recently studies have also shown that halofuginone acts as an agent capable of reducing fibrosis, an indication with clinical relevance for several disease states. This review summarizes historical isolation studies and the chemistry performed which culminated in the correct structural elucidation of naturally occurring Febrifugine and its isomer isofebrifugine. It also includes the range of Febrifugine analogues prepared for antimalarial evaluation, including halofuginone. Finally, a section detailing current opinion in the field of halofuginone's human biology is included.
Febrifugine dihydrochloride as a new oral chemotherapeutic agent against visceral leishmaniasis infection
Exp Parasitol 2022 May-Jun;236-237:108250.PMID:35390313DOI:10.1016/j.exppara.2022.108250.
Visceral leishmaniasis (VL) is the deadliest form of leishmaniasis without a safer treatment option. This study implies drug repurposing to find a novel antileishmanial compound, namely Febrifugine dihydrochloride (FFG) targeting Leishmania antioxidant system. Starting with virtual screening revealed the high binding affinity and lead likeness of FFG against the trypanothione reductase (TR) enzyme of Leishmania donovani, followed by experimental validation. The promastigotes inhibition assay gave the IC50 concentration of FFG and Miltefosine (positive control) as 7.16 ± 1.39 nM and 11.41 ± 0.29 μM, respectively. Their CC50 was found as 451 ± 12.73 nM and 135.9 ± 5.94 μM, respectively. FFG has been shown to increase the reactive oxygen species (ROS), leading to apoptosis-like cell death among L. donovani promastigotes. Spleen touch biopsy resulted in 62% and 55% decreased parasite load with FFG and miltefosine treatment, respectively. Cytokine profiling has shown an increased proinflammatory cytokine response post-FFG treatment. Moreover, FFG is safe on the liver toxicity parameter in mice post-treatment.
[Investigation on stability and degradation kinetics of Febrifugine]
Zhongguo Zhong Yao Za Zhi 2017 Aug;42(16):3178-3184.PMID:29171238DOI:10.19540/j.cnki.cjcmm.2017.0126.
To investigate the stability and degradation kinetics of Febrifugine. The results showed that within 24 hours, Febrifugine content was decreased by only 1% in mobile phase solvent, but its content was decreased to be 90% of the initial content in the water, methanol, 50% methanol and 10% acetonitrile solution. When the pH value of the solution was between 3 and 7, the retention rate of Febrifugine in 24 hours was over 98%, but its content was decreased by about 12% in alkaline solution (pH 9.0). The higher the temperature, the worse the stability of Febrifugine. At 40-80 ℃, the content of Febrifugine was decreased to be 60% of its initial content in 10 hours, but the content was decreased by only 5% in 10 h at 20 ℃.However, no matter 40 ℃or 60 ℃, Febrifugine was mainly transformed into isofebrifugine, and the total content of Febrifugine and isofebrifugine was equal to their initial total content in 10 hours, while incase of 80 ℃, the total content was decreased to be 83.33% in 10 h, which suggested that the structure of Febrifugine was absolutely changed, not just isomerized to be isofebrigugine at high temperature. Light had a significant impact on the stability of Febrifugine. Under bright light, the content of Febrifugine was reduced by about 23% in 108 h, but it only decreased by about 10% in the natural light or darkness. In artificial gastric fluid (pH 1.4) and artificial intestinal fluid (pH 6.8), the content of Febrifugine was decreased by less than 5% in 10 h. After storage at high temperature(60 ℃), high humidity [(75±1)%] and strong light (3 000 lx) conditions for 10 d, the content of solid Febrifugine was decreased by 0.27%, 7.6% and 5.39%, respectively. The degradation of Febrifugine basically complied with the first-order reaction kinetic process in the following conditions: in water, methanol, 50%methanol and 10% acetonitrile solvents, alkaline solution (pH>7), different light intensity and different temperatures (20,40 ℃). Therefore, no matter the isolation and purification of Febrifugine or the production of the related preparations, it should be done fast in the acidic solution, low temperature and dark conditions, while the Febrifugine solid should be kept in dry and dark conditions.