布帕伐醌作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetBuparvaquoneCat. No.: HY-17581CAS No.: 88426-33-9分式: CHO分量: 326.43作靶點: Parasite作通路: Anti-infection儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 33.33 mg/mL (102.10 mM; Need ultrasonic)DMF : 25 mg/mL (76.59 mM; Need ultrasonic)Ethanol : 2 mg/

2、mL (6.13 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 3.0634 mL 15.3172 mL 30.6344 mL5 mM 0.6127 mL 3.0634 mL 6.1269 mL10 mM 0.3063 mL 1.5317 mL 3.0634 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。

3、-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMF 90% (20% SBE-CD in saline)2.Solubility: 2.5 mg/mL (7.66 mM); Clear

4、 solution請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.66 mM); Suspended solution; Need ultrasonic此案可獲得 2.5 mg/mL (7.66 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加Page 1 of 2 www.MedChemE50 L Tween-80，混合均勻；然后繼續(xù)加 450

5、L 理鹽定容 1 mL。3. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.66 mM); Clear solution此案可獲得 2.5 mg/mL (7.66 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。4. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.66 mM); Clear solut

6、ion此案可獲得 2.5 mg/mL (7.66 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Buparvaquone種與parvaquone和atovaquone有關(guān)的羥 萘醌類抗原藥。體外研究 In 4-day proliferation assays, buparvaquone efficiently inhibits N. caninum tachyzoite replication(IC50=4.

7、9 nM; IC100=100 nM)1. Buparvaquone is significantly selective against L. (L.) infantum chagasi intracellular amastigotes, with anIC50 value of 1.5 M. Other cutaneous species are also susceptible to buparvaquone, with IC50 values in the range 1-4M2.體內(nèi)研究 Treatment of N. caninum infected mice with bupa

8、rvaquone (100 mg/kg) either by intraperitoneal injection or gavageprevents neosporosis symptoms in 4 out of 6 mice in the intraperitoneally treated group, and in 6 out of 7 mice in thegroup receiving oral treatment1. Both a hydrous gel and water-in-oil emulsion of buparvaquone significantly reducecu

9、taneous parasite burden and lesion size, compared with the untreated control3.PROTOCOLCell Assay 1 To study whether pretreatment of host cells prior to invasion had any effect on parasite proliferation, confluent HFFgrown in 6-well plates are treated with 1 M buparvaquone in medium for 1 h or 5 h, a

10、nd controls are exposed to thecorresponding amounts of DMSO. Subsequently, the drug-containing medium is removed and monolayers are ished4 times with Hanks Balanced Salt Solution, and are infected with Nc-Liv tachyzoites in 5 mL medium without anydrug or solvent. After 2 days, cells are collected wi

11、th a cell scraper, centrifuged, ished once more in PBS, and thepellet is stored at 20 C prior to quantification of N. caninum proliferation by N. caninum-specific real time PCR asoutlined below1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mic

12、e: On day 0, all mice are infected by intraperitoneal (i.p.) injection of freshly purified N. caninum tachyzoites. AfterAdministration 1 48 h, mice receive BPQ (100 mg/kg) as suspension in corn oil either by i.p. injection of a volume of 100 l or by oralapplication of 100 l by gavage. The control gr

13、oups obtained the corresponding amount of the solvent only, eitheri.p. or orally (see Table 2). The treatments are performed 5 times on a daily basis. If not indicated otherwise, mice areinspected twice daily for clinical signs (ruffled coat, apathy, hind limb paralysis) until day 21 post infection

14、(p.i.), atwhich time they are euthanized1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCESPage 2 of 3 www.MedChemE1. Mller J, et al. Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice. Int J Parasitol

15、Drugs Drug Resist. 2015 Feb13;5(1):16-25.2. Reimo JQ, et al. Effectiveness of liposomal buparvaquone in an experimental hamster model of Leishmania (L.) infantum chagasi. Exp Parasitol. 2012Mar;130(3):195-9.3. Garnier T, et al. In vivo studies on the antileishmanial activity of buparvaquone and its prodrugs. J Antimicrob Chemother. 2007 Oct;60(4):8