Metabolism of 8-aminoquinoline antimalarial agents.
Metabolism of 8-aminoquinoline antimalarial agents.
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8-氨基喹啉抗疟药的代谢。
DOI：
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发表时间：
1981
影响因子：
11.1
通讯作者：
B. E. TnLTON
中科院分区：
文献类型：
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作者：
A. Strother;I. M. Fraser;Reza Allahyari;B. E. TnLTON
一些最有效的抗疟剂是8-氨基喹啉的衍生物。许多这些化合物的代谢产物似乎对某些人类受试者的红细胞有毒性，特别是葡萄糖-6-磷酸脱氢酶缺乏的那些。尽管多年来进行了大量研究，但大多数这些化合物的代谢尚未确定。成年狗给药氚标记伯氨喹后，8小时内约有16%的放射性从尿中排出。通过薄层色谱法对尿液的有机提取物进行分级，并获得代谢模式。部分伯氨喹与至少5种代谢产物（5-羟基-6-甲氧基-8-（4-氨基-1-甲基丁氨基）喹啉（5 HPQ）和少量6-羟基-8-（4-氨基-1-甲基丁氨基）喹啉（6 HPQ））一起沿着排泄。5 HPQ可以形成醌亚胺型化合物，其可能是高铁血红蛋白形成化合物。在体外研究中，发现从尿液中分离的这种代谢物和其他代谢物是活性高铁血红蛋白形成剂。伯氨喹通过小鼠肝酶的体外代谢也产生能够形成高铁血红蛋白的化合物。其中一种在碱性条件、空气和光照下呈蓝色，质谱数据和核磁共振分析表明其结构类似于伯氨喹的5，6-二羟基衍生物。然而，在这些研究中未确定代谢产物的化学结构。
Some of the most effective antimalarial agents are derivatives of 8-aminoquinoline. The metabolic products of many of these compounds appear to be toxic to the erythrocytes of certain human subjects, especially those deficient in glucose-6-phosphate dehydrogenase. Although a number of studies have been conducted over many years, the metabolism of most of these compounds has not been determined. These studies are reviewed.Adult dogs dosed with tritium-labelled primaquine were observed to excrete approximately 16% of the injected radioactivity in the urine within 8 hours. Organic extracts of the urine were fractionated by thin-layer chromatography and the metabolic pattern obtained. Some primaquine was excreted along with at least five metabolites including 5-hydroxy-6-methoxy-8-(4-amino-1-methylbutylamino)quinoline (5HPQ) and a small amount of 6-hydroxy-8-(4-amino-1-methylbutylamino)quinoline (6HPQ). The 5HPQ could form a quinoneimine-type compound which may be a methaemoglobin-forming compound. This and other metabolites isolated from urine were found to be active methaemoglobin formers in in vitro studies. In vitro metabolism of primaquine by mouse liver enzymes also produced compounds capable of methaemoglobin formation. One of these had a blue colour when exposed to alkaline conditions, air, and light, and mass spectral data and nuclear magnetic resonance analysis indicated a structure similar to a 5,6-dihydroxy derivative of primaquine. However, the chemical structure of the metabolite was not identified in these studies.