体外恶性疟原虫中抗疟药物活性、蓄积及对血红素聚合抑制作用之间的关系
Relationship between antimalarial drug activity, accumulation, and inhibition of heme polymerization in Plasmodium falciparum in vitro.
作者信息
Hawley S R, Bray P G, Mungthin M, Atkinson J D, O'Neill P M, Ward S A
机构信息
Department of Human Anatomy and Cell Biology, University of Liverpool, United Kingdom.
出版信息
Antimicrob Agents Chemother. 1998 Mar;42(3):682-6. doi: 10.1128/AAC.42.3.682.
Abstract
We have investigated the contribution of drug accumulation and inhibition of heme polymerization to the in vitro activities of a series of antimalarial drugs. Only those compounds exhibiting structural relatedness to the quinolines inhibited heme polymerization. We could find no direct correlation between in vitro activity against chloroquine-susceptible or chloroquine-resistant isolates and either inhibition of heme polymerization or cellular drug accumulation for the drugs studied. However, in vitro activity against a chloroquine-susceptible isolate but not a chloroquine-resistant isolate showed a significant correlation with inhibition of heme polymerization when the activity was normalized for the extent of drug accumulation. The importance of these observations to the rational design of new quinoline-type drugs and the level of agreement of these conclusions with current views on quinoline drug action and resistance are discussed.
摘要
我们研究了药物蓄积和血红素聚合抑制对一系列抗疟药物体外活性的作用。只有那些与喹啉结构相关的化合物能抑制血红素聚合。对于所研究的药物，我们未发现其对氯喹敏感或氯喹耐药分离株的体外活性与血红素聚合抑制或细胞内药物蓄积之间存在直接关联。然而，当针对药物蓄积程度对活性进行标准化处理时，对氯喹敏感分离株而非氯喹耐药分离株的体外活性与血红素聚合抑制呈现出显著相关性。本文讨论了这些观察结果对于新型喹啉类药物合理设计的重要性以及这些结论与当前关于喹啉类药物作用和耐药性观点的契合程度。
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本文引用的文献
1
The pathway of hemoglobin degradation in malaria parasites.疟原虫中血红蛋白降解的途径。
Parasitol Today. 1992 Aug;8(8):280-3. doi: 10.1016/0169-4758(92)90146-s.
2
COMPLEX FORMATION BETWEEN CHLOROQUINE AND FERRIHAEMIC ACID IN VITRO, AND ITS EFFECT ON THE ANTIMALARIAL ACTION OF CHLOROQUINE.氯喹与高铁血红素在体外的络合形成及其对氯喹抗疟作用的影响。
Nature. 1964 May 23;202:805-6. doi: 10.1038/202805a0.
3
ANTAGONISM OF THE ANTIMALARIAL ACTION OF CHLOROQUINE BY FERRIHEMATE AND AN HYPOTHESIS FOR THE MECHANISM OF CHLOROQUINE RESISTANCE.
J Pharmacol Exp Ther. 1964 Mar;143:278-81.
4
Quinoline resistance mechanisms in Plasmodium falciparum: the debate goes on.恶性疟原虫对喹啉的耐药机制：争论仍在继续。
Parasitology. 1997;114 Suppl:S125-36.
5
Quinoline antimalarials: mechanisms of action and resistance.喹啉类抗疟药：作用机制与耐药性
Int J Parasitol. 1997 Feb;27(2):231-40. doi: 10.1016/s0020-7519(96)00152-x.
6
Synthesis, antimalarial activity, and molecular modeling of tebuquine analogues.替布喹类似物的合成、抗疟活性及分子模拟
J Med Chem. 1997 Feb 14;40(4):437-48. doi: 10.1021/jm960370r.
7
Hemoglobin catabolism and iron utilization by malaria parasites.疟原虫对血红蛋白的分解代谢及铁的利用
Mol Biochem Parasitol. 1996 Dec 20;83(2):131-9. doi: 10.1016/s0166-6851(96)02763-6.
8
Physicochemical properties correlated with drug resistance and the reversal of drug resistance in Plasmodium falciparum.与恶性疟原虫耐药性及耐药逆转相关的物理化学性质。
Mol Pharmacol. 1996 Dec;50(6):1559-66.
9
4-Aminoquinoline resistance of Plasmodium falciparum: insights from the study of amodiaquine uptake.恶性疟原虫对4-氨基喹啉的耐药性：来自阿莫地喹摄取研究的见解
Mol Pharmacol. 1996 Dec;50(6):1551-8.
10
Manipulation of the N-alkyl substituent in amodiaquine to overcome the verapamil-sensitive chloroquine resistance component.对阿莫地喹中的N-烷基取代基进行操作以克服维拉帕米敏感的氯喹抗性成分。
Antimicrob Agents Chemother. 1996 Oct;40(10):2345-9. doi: 10.1128/AAC.40.10.2345.
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