Buparvaquone
(Synonyms: 布帕伐醌) 目录号 : GC35569
An electron transport chain inhibitor
Cas No.:88426-33-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | To study whether pretreatment of host cells prior to invasion had any effect on parasite proliferation, confluent HFF grown in 6-well plates are treated with 1 µM buparvaquone in medium for 1 h or 5 h, and controls are exposed to the corresponding amounts of DMSO. Subsequently, the drug-containing medium is removed and monolayers are ished 4 times with Hank's Balanced Salt Solution, and are infected with Nc-Liv tachyzoites in 5 mL medium without any drug or solvent. After 2 days, cells are collected with a cell scraper, centrifuged, ished once more in PBS, and the pellet is stored at −20 °C prior to quantification of N. caninum proliferation by N. caninum-specific real time PCR as outlined below[1]. |
Animal experiment: | Mice: On day 0, all mice are infected by intraperitoneal (i.p.) injection of freshly purified N. caninum tachyzoites. After 48 h, mice receive BPQ (100 mg/kg) as suspension in corn oil either by i.p. injection of a volume of 100 µl or by oral application of 100 µl by gavage. The control groups obtained the corresponding amount of the solvent only, either i.p. or orally (see Table 2). The treatments are performed 5 times on a daily basis. If not indicated otherwise, mice are inspected twice daily for clinical signs (ruffled coat, apathy, hind limb paralysis) until day 21 post infection (p.i.), at which time they are euthanized[1]. |
References: [1]. Müller J, et al. Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice. Int J Parasitol Drugs Drug Resist. 2015 Feb 13;5(1):16-25. | |
Buparvaquone is a hydroxynaphthoquinone that inhibits electron transport by blocking cytochrome bc1 in parasites that cause leishmaniasis.1 Formulations containing buparvaquone are used to treat theileriosis, an infection by the parasites T. annulata and T. parva (in vitro EC50s of 1.5 x 10-8 M and 6.1 x 10-10 M, respectively).2,3
1.Ortiz, D., Forquer, I., Boitz, J., et al.Targeting the cytochrome bc1 complex of Leishmania parasites for discovery of novel drugsAntimicrob. Agents and Chemother.60(8)4972-4982(2016) 2.Abdou, T.A., Abou-El-naga, T.R., and Mahmoud, M.A.Clinicopathological studies on Theileria annulata infection in Siwa oasis in Egypt56th Annual Meeting of the European Association for Animal Production70(2005) 3.Hudson, A.T., Randall, A.W., Fry, M., et al.Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum anti-protozoal activityParasitology90(Pt 1)45-55(1985)
| Cas No. | 88426-33-9 | SDF | |
| 别名 | 布帕伐醌 | ||
| Canonical SMILES | O=C1C(CC2CCC(C(C)(C)C)CC2)=C(O)C(C3=C1C=CC=C3)=O | ||
| 分子式 | C21H26O3 | 分子量 | 326.43 |
| 溶解度 | DMSO: 33.33 mg/mL (102.10 mM); DMF: 25 mg/mL (76.59 mM); Ethanol: 2 mg/mL (6.13 mM); Water: < 0.1 mg/mL (insoluble) | 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 | 3.0634 mL | 15.3172 mL | 30.6344 mL |
| 5 mM | 0.6127 mL | 3.0634 mL | 6.1269 mL |
| 10 mM | 0.3063 mL | 1.5317 mL | 3.0634 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。
Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice
Int J Parasitol Drugs Drug Resist 2015 Feb 13;5(1):16-25.PMID:25941626DOI:10.1016/j.ijpddr.2015.02.001.
The naphthoquinone Buparvaquone is currently the only drug used against theileriosis. Here, the effects of Buparvaquone were investigated in vitro and in an experimental mouse model for Neospora caninum infection. In 4-day proliferation assays, Buparvaquone efficiently inhibited N. caninum tachyzoite replication (IC50 = 4.9 nM; IC100 = 100 nM). However, in the long term tachyzoites adapted and resumed proliferation in the presence of 100 nM Buparvaquone after 20 days of cultivation. Parasiticidal activity was noted after 9 days of culture in 0.5 µM or 6 days in 1 µM Buparvaquone. TEM of N. caninum infected fibroblasts treated with 1 µM Buparvaquone showed that the drug acted rather slowly, and ultrastructural changes were evident only after 3-5 days of treatment, including severe alterations in the parasite cytoplasm, changes in the composition of the parasitophorous vacuole matrix and a diminished integrity of the vacuole membrane. Treatment of N. caninum infected mice with Buparvaquone (100 mg/kg) either by intraperitoneal injection or gavage prevented neosporosis symptoms in 4 out of 6 mice in the intraperitoneally treated group, and in 6 out of 7 mice in the group receiving oral treatment. In the corresponding controls, all 6 mice injected intraperitoneally with corn oil alone died of acute neosporosis, and 4 out of 6 mice died in the orally treated control group. Assessment of infection intensities in the treatment groups showed that, compared to the drug treated groups, the controls showed a significantly higher parasite load in the lungs while cerebral parasite load was higher in the buparvaquone-treated groups. Thus, although Buparvaquone did not eliminate the parasites infecting the CNS, the drug represents an interesting lead with the potential to eliminate, or at least diminish, fetal infection during pregnancy.
Concentrations of Buparvaquone in milk and tissue of dairy cows
N Z Vet J 2016 Nov;64(6):318-23.PMID:27373797DOI:10.1080/00480169.2016.1204960.
Aim: To determine the concentration of the anti-theilerial drug Buparvaquone in the milk and tissue of dairy cattle following treatment with two different formulations, and to assess the effect of clinical theileriosis on the concentration of Buparvaquone in milk. Methods: Healthy lactating dairy cows (n=25) were injected once (Day 0) I/M with 2.5 mg/kg of one of two formulations of Buparvaquone (Butalex; n=12 or Bupaject; n=13). Milk samples were collected from all cows daily until Day 35. Five cows were slaughtered on each of Days 56, 119, 147, 203 and 328, and samples of liver, muscle and injection site tissue collected. Milk samples were also collected from cows (n=14) clinically affected with theileriosis for up to 21 days after treatment with Buparvaquone. Milk and tissue samples were analysed by liquid chromatography-mass spectrometry; limits of detection (LOD) were 0.00018 mg/kg for muscle and 0.00023 mg/L for milk. Concentrations of Buparvaquone in milk and tissues were log10-transformed for analysis using multivariate models. Results: In healthy cows, concentrations of Buparvaquone in milk declined with time post-treatment (p<0.001), but were above the LOD in 11 of 25 cows at Day 35. Concentration in milk was higher one day after treatment in cows treated with Butalex than in cows treated with Bupaject, but not different thereafter (p=0.007). Concentrations of Buparvaquone in muscle were below the LOD for four of five animals at Day 119 and for all animals by Day 147, but were above the LOD at the injection site of one cow, and in the liver of three cows at Day 328. Tissue concentrations did not differ with formulation nor was there a formulation by time interaction (p>0.3). Concentrations of Buparvaquone in the milk of clinically affected animals were not different from those of healthy animals at 1 and 21 days post-treatment (p=0.72). Between 21 and 25 days post-treatment concentrations were below the LOD in 9/14 milk samples from clinically affected cows. Conclusions: Detectable concentrations of Buparvaquone were found in the milk of some cows for at least 35 days and in the liver and injection site of some cows until at least 328 days after injection. There were no biologically meaningful differences in milk or tissue concentrations between the formulations, or in the milk concentrations for cows that were clinically affected compared with those that were healthy at the time of treatment.
Topical Buparvaquone nano-enabled hydrogels for cutaneous leishmaniasis
Int J Pharm 2020 Oct 15;588:119734.PMID:32777535DOI:10.1016/j.ijpharm.2020.119734.
Leishmaniasis is a neglected disease presenting cutaneous, mucosal and visceral forms and affecting an estimated 12 million mostly low-income people. Treatment of cutaneous leishmaniasis (CL) is recommended to expedite healing, reduce risk of scarring, prevent parasite dissemination to other mucocutaneous (common with New World species) or visceral forms and reduce the chance of relapse, but remains an unmet need. Available treatments are painful, prolonged (>20 days) and require hospitalisation, which increases the cost of therapy. Here we present the development of optimised topical self-nanoemulsifying drug delivery systems (SNEDDS) loaded with Buparvaquone (BPQ, a hydroxynapthoquinone from the open Malaria Box) for the treatment of CL from New World species. The administration of topical BPQ-SNEDDS gels for 7 days resulted in a reduction of parasite load of 99.989 ± 0.019% similar to the decrease achieved with intralesionally administered Glucantime® (99.873 ± 0.204%) in a L. amazonensis BALB/c model. In vivo efficacy was supported by ex vivo permeability and in vivo tape stripping studies. BPQ-SNEDDS and their hydrogels demonstrated linear flux across non-infected CD-1 mouse skin ex vivo of 182.4 ± 63.0 μg cm-2 h-1 and 57.6 ± 10.8 μg cm-2 h-1 respectively localising BPQ within the skin in clinically effective concentrations (227.0 ± 45.9 μg and 103.8 ± 33.8 μg) respectively. These levels are therapeutic as BPQ-SNEDDS and their gels showed nanomolar in vitro efficacy against L. amazonensis and L. braziliensis amastigotes with excellent selectivity index toward parasites versus murine macrophages. In vivo tape stripping experiments indicated localisation of BPQ within the stratum corneum and dermis. Histology studies confirmed the reduction of parasitism and indicated healing in animals treated with BPQ-SNEDDS hydrogels. These results highlight the potential clinical capability of nano-enabled BPQ hydrogels towards a non-invasive treatment for CL.
In Vitro and In Vivo Antifungal Activity of Buparvaquone against Sporothrix brasiliensis
Antimicrob Agents Chemother 2021 Aug 17;65(9):e0069921.PMID:34152816DOI:10.1128/AAC.00699-21.
Sporotrichosis has become an important zoonosis in Brazil, and Sporothrix brasiliensis is the primary species transmitted by cats. Improvement of animal treatment will help control and limit the spread and geographic expansion of sporotrichosis. Accordingly, Buparvaquone, an antiprotozoal hydroxynaphthoquinone agent marketed as Butalex, was evaluated in vitro and in vivo against feline-borne isolates of S. brasiliensis. Buparvaquone inhibited in vitro fungal growth at concentrations 4-fold lower than itraconazole (the first-choice antifungal used for sporotrichosis) and was 408 times more selective for S. brasiliensis than mammalian cells. Yeasts treated with a subinhibitory concentration of Buparvaquone exhibited mitochondrial dysfunction, reactive oxygen species and neutral lipid accumulation, and impaired plasma membranes. Scanning electron microscopy images also revealed Buparvaquone altered cell wall integrity and induced cell disruption. In vivo experiments in a Galleria mellonella model revealed that Buparvaquone (single dose of 5 mg/kg of body weight) is more effective than itraconazole against infections with S. brasiliensis yeasts. Combined, our results indicate that Buparvaquone has a great in vitro and in vivo antifungal activity against S. brasiliensis, revealing the potential application of this drug as an alternative treatment for feline sporotrichosis.
Trifloxystrobin blocks the growth of Theileria parasites and is a promising drug to treat Buparvaquone resistance
Commun Biol 2022 Nov 15;5(1):1253.PMID:36380082DOI:10.1038/s42003-022-03981-x.
Theileria parasites are responsible for devastating cattle diseases, causing major economic losses across Africa and Asia. Theileria spp. stand apart from other apicomplexa parasites by their ability to transform host leukocytes into immortalized, hyperproliferating, invasive cells that rapidly kill infected animals. The emergence of resistance to the theilericidal drug Buparvaquone raises the need for new anti-Theileria drugs. We developed a microscopy-based screen to reposition drugs from the open-access Medicines for Malaria Venture (MMV) Pathogen Box. We show that Trifloxystrobin (MMV688754) selectively kills lymphocytes or macrophages infected with Theileria annulata or Theileria parva parasites. Trifloxystrobin treatment reduced parasite load in vitro as effectively as Buparvaquone, with similar effects on host gene expression, cell proliferation and cell cycle. Trifloxystrobin also inhibited parasite differentiation to merozoites (merogony). Trifloxystrobin inhibition of parasite survival is independent of the parasite TaPin1 prolyl isomerase pathway. Furthermore, modeling studies predicted that Trifloxystrobin and Buparvaquone could interact distinctly with parasite Cytochrome B and we show that Trifloxystrobin was still effective against Buparvaquone-resistant cells harboring TaCytB mutations. Our study suggests that Trifloxystrobin could provide an effective alternative to Buparvaquone treatment and represents a promising candidate for future drug development against Theileria spp.