OXYGEN-DEPENDENT AND TIME-DEPENDENT EFFECTS OF ANTIBIOTICS AND SELECTED MITOCHONDRIAL INHIBITORS ON PLASMODIUM-FALCIPARUM IN CULTURE
OXYGEN-DEPENDENT AND TIME-DEPENDENT EFFECTS OF ANTIBIOTICS AND SELECTED MITOCHONDRIAL INHIBITORS ON PLASMODIUM-FALCIPARUM IN CULTURE
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DOI：
10.1128/aac.27.1.21
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发表时间：
1985-01-01
影响因子：
4.9
通讯作者：
JENSEN, JB
中科院分区：
文献类型：
--
作者：
DIVO, AA;GEARY, TG;JENSEN, JB
克林霉素、吡利霉素、4“-戊基-N-去甲基克林霉素、四环素、氯霉素、甲砜霉素和红霉素等几种抑制70 S核糖体蛋白合成的抗生素对培养的恶性疟原虫有抗疟作用，其作用受药物暴露时间和氧分压的影响很大。在96小时孵育中，在前48小时内效价增加了106倍，在15% O2与1% O2中增加了104倍。两种氨基糖苷类抗生素卡那霉素和妥布霉素无抗疟活性。抑制核酸合成的利福平和萘啶酸与70 S抑制剂不相似。线粒体抑制剂Janus绿色、罗丹明123、抗霉素A1和8-甲氨基-8-去甲基核黄素的活性受暴露时间和O2张力的影响。含喹啉类抗疟药、离子载体和其他抗疟药受暴露时间的影响较小，但不受O2张力的影响。这些数据可以最好地解释的假设，即抗疟疾70 S核糖体特异性蛋白质合成抑制剂是有毒的寄生虫通过作用于peption。
Several antibiotics which inhibit protein synthesis on 70S ribosomes, including clindamycin, pirlimycin, 4''-pentyl-N-demethylclindamycin, 4 tetracyclines, chloramphenicol, thiamphenicol and erythromycin, had antimalarial effects against P. falciparum in culture which were greatly influenced by the duration of drug exposure and by O2 tension. In 96-h incubations, potency was increased by a factor of up to 106 over the first 48-h period and by a factor of up to 104 in 15% O2 vs 1% O2. Two aminoglycosides, kanamycin and tobramycin, had no antimalarial activity. Rifampin and nalidixic acid, which inhibit nucleic acid synthesis, were not similar to the 70S inhibitors. The mitochondrial inhibitors Janus Green, rhodamine 123, antimycin A1 and 8-methylamino-8-desmethylriboflavin had activities which were influenced by the duration of exposure and O2 tension. Quinoline-containing antimalarial agents, ionophores and other antimalarial drugs were influenced to a minor extent by the duration of exposure but were not affected by O2 tension. These data can best be explained by the hypothesis that antimalarial 70S ribosome-specific protein synthesis inhibitors are toxic to the parasites by acting on the mitochondrion.