Proguanil 是一种抗疟前药,被代谢为活性代谢物环鸟苷 (HY-12784)。Proguanil 是一种二氢叶酸还原酶 (DHFR) 抑制剂。
生物活性 | Proguanil, an antimalarial prodrug, is metabolized to the active metabolite Cycloguanil (HY-12784). Proguanil is adihydrofolate reductase(DHFR) inhibitor[1][2]. |
体外研究 (In Vitro) | Proguanil per se has only weak antimalarial activityin vitro(IC50=2.4-19 μM), and its effectiveness depends on the active metabolite Cycloguanil (IC50=0.5-2.5 nM). The Cycloguanil is a dihydrofolate reductase (DHFR) inhibitor. The combination of Atovaquone and Proguanil is synergisticin vitro. Both drugs also have activity against gametocytes and pre-erythrocytic (hepatic) stages of malaria parasites[1]. Proguanil acts as a biguanide rather than as its metabolite Cycloguanil (a parasite dihydrofolate reductase [DHFR] inhibitor) to enhance the Atovaquone effect. Proguanil-mediated enhancement is specific for Atovaquone, since the effects of other mitochondrial electron transport inhibitors, such as Myxothiazole and Antimycin, are not altered by inclusion of Proguanil[2]. 5-HT3receptor responses are reversibly inhibited by Proguanil, the metabolite 4-chlorophenyl-1-biguanide (CPB) and the active metabolite Cycloguanil (CG), with an IC50of 1.81, 1.48 and 4.36 μM, respectively[3].
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体内研究 (In Vivo) | Proguanil (p.o.; 2.9 mg/kg body weight; daily for 5 days and 6 weeks respectively) shows mild degenerative changes for five days, while shows severe degenerative changes for six weeks in wistar strain albino rats[4]. Serum testosterone level is significantly decreased for proguanil treatment rats[4]. Administration of Malarone (atovaquone and proguanil) to experimentallyB. gibsoniinfected two dogs in chronic stage and three dogs in acute stage results in decrease in parasitemia, and clinical improvements are observed[5].
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : ≥ 130 mg/mL(512.36 mM) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 3.9412 mL | 19.7060 mL | 39.4120 mL | 5 mM | 0.7882 mL | 3.9412 mL | 7.8824 mL | 10 mM | 0.3941 mL | 1.9706 mL | 3.9412 mL |
*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℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.17 mg/mL (8.55 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (8.55 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.17 mg/mL (8.55 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (8.55 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.17 mg/mL (8.55 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (8.55 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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