青蒿琥酯在水介质中被血红素激活。
Artesunate Activation by Heme in an Aqueous Medium.
作者信息
Heller Laura, Roepe Paul D, de Dios Angel C
机构信息
Dept. of Chemistry, Georgetown University, 37 and O Streets, Washington, DC.
Dept, of Biochemistry and Cellular & Molecular Biology, Georgetown University, 37 and O Streets, Washington, DC.
出版信息
Inorganica Chim Acta. 2019 Oct 1;496. doi: 10.1016/j.ica.2019.119029. Epub 2019 Jul 22.
The reaction between the antimalarial drug artesunate (ATS) and ferriprotoporphyrin_(IX) (FPIX) in the presence of glutathione (GSH) has been monitored by nuclear magnetic resonance (NMR) spectroscopy. By following the disappearance of resonances of protons near the endoperoxide group in ATS, the rate at which the drug is activated can be directly measured. In an aqueous medium, the rate of ATS activation is limited by the rate of reduction of the FPIX Fe(III) center by GSH. The reaction is observed to slow dramatically in the presence of other heme binding antimalarial drugs. These findings explain the long observed antagonism between artemisinin derivatives and quinoline-based drugs. This discovery suggests that combination therapy that involves artemisinin or any of its derivatives and a quinoline-based drug may be compromised.
在谷胱甘肽（GSH）存在的情况下，通过核磁共振（NMR）光谱监测了抗疟药物青蒿琥酯（ATS）与亚铁原卟啉_（IX）（FPIX）之间的反应。通过跟踪ATS中内过氧化物基团附近质子共振的消失，可以直接测量药物的活化速率。在水性介质中，ATS的活化速率受GSH对FPIX Fe（III）中心还原速率的限制。在其他血红素结合抗疟药物存在的情况下，观察到反应显著减慢。这些发现解释了长期以来观察到的青蒿素衍生物与喹啉类药物之间的拮抗作用。这一发现表明，涉及青蒿素或其任何衍生物与喹啉类药物的联合疗法可能会受到影响。
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