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首页> 外文期刊>The American Journal of Tropical Medicine and Hygiene >Effect of pH on in vitro potency of amantadine against Plasmodium falciparum.
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Effect of pH on in vitro potency of amantadine against Plasmodium falciparum.

机译：pH值对金刚烷胺体外抗恶性疟原虫效力的影响。

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摘要

Amantadine is a monoprotic weak base that inhibits intraerythrocytic growth in in vitro cultures of Plasmodium falciparum, specifically chloroquine-resistant strains. Changes in the external PH of the medium are expected to result in a shift in the relative proportion of ionized and unionized species of amantadine by virtue of the weak base characteristic of the drug, influencing passage of the drug through the membrane. The ability of amantadine to alkalinize the food vacuole was determined using the accumulation of acridine orange as a vacuolar probe. Drug sensitivity following alteration of the pH gradient was assessed using the hypoxanthine method. Amantadine was able to alkalinize the food vacuole in the millimolar range; however, since its antimalarial activity is in the micromolar range, alkalinization of the food vacuole is not the primary action of the drug. The pH of the medium profoundly influenced susceptibility to chloroquine; the log of the 50% inhibitory concentration (IC50) values were linearly dependent on the external pH in both chloroquine-resistant and chloroquine-sensitive strains. Log IC50 values of amantadine exhibited a linear dependence on external pH in the chloroquine-sensitive strain, but in the chloroquine-resistant strain, a nonlinear parabolic function was found with the minimum IC50 at pH 7.03. Ammonium chloride did not interfere with the antimalarial activity of amantadine. The presence of the amine group on the hydrocarbon cage is essential for the activity of amantadine in Plasmodium falciparum. These results suggest factors in addition to pH gradient are involved in the effect of amantadine, possibly interactions with membrane phospholipids.
机译：金刚烷胺是单质子性弱碱，在恶性疟原虫，特别是对氯喹抗性菌株的体外培养中抑制红细胞内生长。由于药物的弱碱特性，预计培养基外部PH的变化会导致金刚烷胺的离子化和工会化种类的相对比例发生变化，从而影响药物通过膜的通过。金刚烷胺碱化食物液泡的能力通过使用of啶橙的积累作为液泡探针来确定。使用次黄嘌呤方法评估pH梯度变化后的药物敏感性。金刚烷胺能够在毫摩尔范围内碱化食物液泡。但是，由于其抗疟疾活性在微摩尔范围内，因此食品液泡的碱化不是该药物的主要作用。培养基的pH值深刻影响了对氯喹的敏感性。在抗氯喹和对氯喹敏感的菌株中，50％抑制浓度（IC50）值的对数线性依赖于外部pH。金刚烷胺的log IC50值在氯喹敏感菌株中表现出对外部pH的线性依赖性，但在耐氯喹菌株中，发现非线性抛物线函数，在pH 7.03时IC50最小。氯化铵不干扰金刚烷胺的抗疟活性。碳氢化合物笼中胺基的存在对于恶性疟原虫中金刚烷胺的活性至关重要。这些结果表明，除了pH梯度以外，金刚烷胺的作用还涉及其他因素，可能与膜磷脂相互作用。

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