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首页> 外文期刊>Life sciences >Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs [Review]
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Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs [Review]

机译：铁原卟啉IX，磷脂和喹啉类药物的抗疟作用[综述]

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Two subclasses of quinoline antimalarial drugs are used clinically. Both act on the endolysosomal system of malaria parasites, but in different ways. Treatment with 4-aminoquinoline drugs, such as chloroquine, causes morphologic changes and hemoglobin accumulation in endocytic vesicles. Treatment with quinoline-4-methanol drugs, such as quinine and mefloquine, also causes morphologic changes, but does not cause hemoglobin accumulation. In addition, chloroquine causes undimerized ferriprotoporphyrin IX (ferric heme) to accumulate whereas quinine and mefloquine do not. On the contrary, treatment with quinine or mefloquine prevents and reverses chloroquine-induced accumulation of hemoglobin and undimerized ferriprotoporphyrin IX. This difference is of particular interest since there is convincing evidence that undimerized ferriprotoporphyrin IX in malaria parasites would interact with and serve as a target for chloroquine. According to the ferriprotoporphyrin IX interaction hypothesis, chloroquine would bind to undimerized ferriprotoporphyrin IX, delay its detoxification, cause it to accumulate, and allow it to exert its intrinsic biological toxicities. The ferriprotoporphyrin IX interaction hypothesis appears to explain the antimalarial action of chloroquine, but a drug target in addition to ferriprotoporphyrin IX is suggested by the antimalarial actions of quinine and mefloquine. This article summarizes current knowledge of the role of ferriprotoporphyrin IX in the antimalarial actions of quinoline drugs and evaluates the currently available evidence in support of phospholipids as a second target for quinine, mefloquine and, possibly, the chloroquine-ferriprotoporphyrin IX complex. (C) 2003 Elsevier Inc. All rights reserved. [References: 135]
机译：临床上使用喹啉类抗疟药的两个亚类。两者都对疟原虫的溶酶体系统起作用，但是方式不同。用4-氨基喹啉药物（例如氯喹）进行治疗会导致内吞囊泡形态变化和血红蛋白积聚。用奎宁-4-甲醇药物（例如奎宁和甲氟喹）进行治疗也可引起形态变化，但不会引起血红蛋白积聚。另外，氯喹导致未二聚的铁原卟啉IX（铁血红素）积聚，而奎宁和甲氟喹则不会积聚。相反，用奎宁或甲氟喹治疗可预防和逆转氯喹诱导的血红蛋白和未二聚的铁原卟啉IX的蓄积。由于存在令人信服的证据，疟疾寄生虫中未二聚的亚铁原卟啉IX会与氯喹相互作用并充当氯喹的靶标，因此这种差异特别令人关注。根据铁原卟啉IX相互作用的假设，氯喹会与未二聚的铁原卟啉IX结合，延迟其解毒作用，使其积累，并发挥其固有的生物毒性。亚铁原卟啉IX相互作用的假说似乎可以解释氯喹的抗疟作用，但是奎宁和甲氟喹的抗疟作用提示除铁原卟啉IX以外的药物靶标。本文总结了有关铁原卟啉IX在喹啉药物的抗疟作用中的作用的当前知识，并评估了目前支持磷脂作为奎宁，甲氟喹以及可能的氯喹-铁原卟啉IX复合物的第二目标的证据。 （C）2003 Elsevier Inc.保留所有权利。 [参考：135]

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