| CAS |
No.171228-49-2 |
| 中文名称 |
泊沙康唑(10mM in DMSO,无菌） |
| 英文名称 |
Posaconazole(10mM in DMSO，Sterile） |
| 分子式 |
C37H42F2N8O4 |
| 分子量 |
700.78 |
| 溶解性 |
请根据自己的实验要求使用。 |
| 外观(性状) |
无菌溶液 |
| 储存条件 |
Stroe at -20℃，6 months. |
| 靶点 |
Fungal |
| 通路 |
Anti-infection |
| 背景说明 |
Posaconazole 是一种广谱的，二代三唑类物质，具有抗真菌活性。 |
| 生物活性 |
Posaconazole is a broad-spectrum， second generation， triazole compound with antifungal activity.[1-5] |
| In Vitro |
Posaconazole 具有强大的杀锥虫活性。胺碘酮与 Posaconazole 协同作用。Posaconazole 还会影响和破坏 T. cruzi 中的 Ca2+ 稳态。Posaconazole 阻断麦角固醇的生物合成，麦角固醇是寄生虫存活所必需的。Posaconazole 对上鞭毛体 (细胞外) 阶段的增殖具有明显的剂量依赖性作用，最小抑制浓度为 20 nM，IC50 为 14 nM。对于寄生虫的临床相关细胞内无鞭毛体形式，Posaconazole 甚至更有效。Posaconazole 具有最小抑制浓度和 IC50 值，分别为 3 nM 和 0.25 nM[1]。Posaconazole 对念珠菌和曲霉属的分离株有活性。对氟康唑、伏立康唑和两性霉素 B 表现出耐药性，并且比其他三唑对接合菌的活性强得多[2]。 |
| In Vivo |
仅用胺碘酮处理受感染的动物可减少寄生虫血症，增加感染后 60 天的存活率 (未处理的对照组为 0%，胺碘酮处理的动物为 40%)，并且当与 Posaconazole 联合使用时，可延缓寄生虫血症的发展[1]。与在禁食状态下单独服用 Posaconazole 相比，Posaconazole 和 Boost Plus 的共同服用增加了药物暴露。食物，尤其是脂肪含量高的食物，可显著增加 Posaconazole 的生物利用度。当与高脂肪和脱脂膳食一起食用时，Posaconazole 的全身暴露量分别增加 4 倍和 2.6 倍[3]。Posaconazole 和胺碘酮可能构成有效的抗 T。cruzi 疗法，副作用小[4]。每天两次剂量≥ 15 mg/kg 体重时，Posaconazole 可延长小鼠的存活时间并减轻组织负荷[5]。 |
| 细胞实验 |
The epimastigote form of the parasite is cultivated in liver infusion tryptose medium，12 supplemented with 10% new born calf serum at 28°C with strong (120 rpm) agitation. Cultures are initiated at a cell density of 2×106 epimastigotes mL-1， and drugs are added at a cell density of 0.5?1.0 ×107 epimastigotes mL-1. Cell densities are measured by using an electronic particle counter as well as by direct counting with a hemocytometer. Cell viability is followed by Trypan blue exclusion， using light microscopy. Amastigotes are cultured in Vero cells maintained in minimal essential medium supplemented with 1% fetal calf serum in a humidified atmosphere (95% air?5% CO2) at 37°C， as described previously. Cells are infected with 10 tissue culture-derived trypomastigotes per cell for 2 h and then washed three times with phosphate-buffered saline (PBS) to remove nonadherent parasites. Fresh medium with and without drugs is added， and the cells are incubated for 96 h with a medium change at 48 h. The percent of infected cells and the numbers of parasites per cell are determined directly using light microscopy， and a statistical analysis of the results is carried out as described previously. IC50 values are calculated by nonlinear regression， using the program GraFit. Cytoplasmic free Ca2+ concentrations in control and drug-treated extracellular epimastigotes are determined by fluorimetric methods， using Fura-2， again as described previously. Subcellular Ca2+ levels and mitochondrial membrane potentials are monitored on individual Vero cells infected with T. cruzi amastigotes by using time-scan confocal microscopy， as described in detail elsewhere. Briefly， Vero cells heavily infected (72 h) with T. cruzi amastigotes are plated onto 22×40 mm glass coverslips (0.15 mm thickness) and incubated simultaneously with 10 μM cell-permeant Rhod-2 and 10 μg/mL Rhodamine-123 for 50 min at 37°C in culture medium and then washed and incubated with Ringer‘s solution， with or without amiodarone. Under the conditions used， fluorescence of Rhod-2 comes mainly from intracellular Ca2+-rich compartments， like mitochondria， since its low affinity for Ca2+ limits its fluorescence in the Ca2+-poor cytoplasm of the Vero cells or amastigotes. Rhodamine-123 is a mitochondrion-specific cationic dye， which distributes across the inner mitochondrial membranes strictly according to their membrane potential. |
| 动物实验 |
In vivo studies are carried out by using the murine model of acute Chagas‘ disease in which female NMRI?IVIC mice (20?25 g) are infected with 105 or 103 bloodstream trypomastigotes and drug treatment is started 24 h later. Treatments are given for 30 consecutive days at 20 mg/kg/d for posaconazole (30 doses) and/or at 50 mg/kg every other day for amiodarone (15 doses). Negative controls (i.e. untreated animals) receive only the vehicle， while positive controls are treated with the anti-T. cruzi compound， nifurtimox， at 50 mg/kg/d for 30 days. Survival is followed daily and parasitemia weekly， the latter by direct microscopic examination. Animals are observed for 60 days postinfection， after which time parasitological cures are evaluated by using a combination of hemoculture， xenodiagnosis， and blood PCR tests. |
| 数据来源文献 |
[1]. Benaim G， et al. Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole. J Med Chem. 2006 Feb 9;49(3):892-9.
[2]. Sabatelli F， et al. In vitro activities of posaconazole， fluconazole， itraconazole， voriconazole， and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother. 2006 Jun;50(6):2009-15.
[3]. Sansone-Parsons A， et al. Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers. Antimicrob Agents Chemother. 2006 May;50(5):1881-3.
[4]. Veiga-Santos P， et al. Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi. Int J Antimicrob Agents. 2012 Jul;40(1):61-71.
[5]. Sun QN， et al. In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model. Antimicrob Agents Chemother. 2002 Jul;46(7):2310-2. |
| 规格 |
1ml |
| 单位 |
瓶 |
中文
英语
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