Thermodynamic factors controlling the interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX
Thermodynamic factors controlling the interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX
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DOI：
10.1016/s0162-0134(97)00086-x
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发表时间：
1997-11-01
影响因子：
3.9
通讯作者：
Marques, HM
中科院分区：
文献类型：
--
作者：
Egan, TJ;Mavuso, WW;Marques, HM
各种喹啉抗疟药物以及其他喹啉衍生物与严格单体铁原卟啉IX [Fe（III）PPIX]的相互作用已在40%的DMSO水溶液中进行了研究。在7.5的表观pH和25 ℃下，结合的log K值为5.52 +/- 0.03（氯喹）、5.39 +/- 0.04（阿莫地喹）、4.10 +/- 0.02（奎宁）、4.04 +/- 0.03（9-表奎宁）和3.90 +/- 0.08（甲氟喹）。伯氨喹、8-羟基喹啉、5-氨基喹啉、6-氨基喹啉、8-氨基喹啉和喹啉没有表现出与Fe（III）PPIX相互作用的证据。喹啉与Fe（III）PPIX的相互作用的焓和熵的变化，确定从温度依赖性的日志K值，表现出的补偿现象，这是暗示的疏水相互作用。这是支持的发现，氯喹和奎宁与铁（III）PPIX的相互作用被削弱的乙腈浓度增加。氯喹、奎宁和9-表奎宁与Fe（III）PPIX的相互作用显示在pH 5.6（疟疾寄生虫的食物泡的近似pH，其被认为是药物活性的场所）下保持强。抗疟药物的设计的影响进行了简要讨论。(C)1997年爱思唯尔科学公司
The interaction of a variety of quinoline antimalarial drugs as well as other quinoline derivatives with strictly monomeric ferriprotoporphyrin IX [Fe(III)PPIX] has been investigated in 40% aqueous DMSO solution. At an apparent pH of 7.5 and 25 degrees C, log K values for bonding are 5.52 +/- 0.03 (chloroquine), 5.39 +/- 0.04 (amodiaquine), 4.10 +/- 0.02 (quinine), 4.04 +/- 0.03 (9-epiquinine), and 3.90 +/- 0.08 (mefloquine). Primaquine, 8-hydroxyquinoline, 5-aminoquinoline, 6-aminoquinoline, 8-aminoquinoline, and quinoline exhibit no evidence of interaction with Fe(III)PPIX. The enthalpy and entropy changes for the interaction of quinolines with Fe(III)PPIX, as determined from the temperature dependence of the log K values, exhibit a compensation phenomenon that is suggestive of hydrophobic interaction. This is supported by the finding that the interactions of chloroquine and quinine with Fe(III)PPIX are weakened by increasing concentrations of acetonitrile. Interactions of chloroquine, quinine, and 9-epiquinine with Fe(lll)PPIX are shown to remain strong at pH 5.6, the approximate pH of the food vacuole of the malaria parasite which is believed to be the locus of drug activity. Implications for the design of antimalarial drugs are briefly discussed. (C) 1997 Elsevier Science Inc.