理解抗疟药抗性难治性黄烷醌 A1 的抗疟作用。
Understanding the Antiplasmodial Action of Resistance-Refractory Xanthoquinodin A1.
机构信息
Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, Florida 32826, United States.
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California 92093, United States.
出版信息
ACS Infect Dis. 2024 Jun 14;10(6):2276-2287. doi: 10.1021/acsinfecdis.4c00232. Epub 2024 May 29.
Our previous work identified a series of 12 xanthoquinodin analogues and 2 emodin-dianthrones with broad-spectrum activities against , , , and . Analyses conducted in this study revealed that the most active analogue, xanthoquinodin A1, also inhibits tachyzoites and the liver stage of , with no cross-resistance to the known antimalarial targets PfACS, PfCARL, PfPI4K, or DHODH. In , inhibition occurs prior to multinucleation and induces parasite death following 12 h of compound exposure. This moderately fast activity has impeded resistance line generation, with xanthoquinodin A1 demonstrating an irresistible phenotype in both and .
我们之前的工作鉴定了一系列 12 种蒽醌二蒽酮类似物和 2 种大黄素-二蒽酮，它们对 、 、 和 具有广谱活性。本研究中的分析表明，最活跃的类似物，即蒽醌二蒽酮 A1，也抑制 速殖子和 肝期，与已知的抗疟靶点 PfACS、PfCARL、PfPI4K 或 DHODH 没有交叉耐药性。在 中，抑制作用发生在多核化之前，并在化合物暴露 12 小时后诱导寄生虫死亡。这种中等快速的活性阻碍了耐药性的产生，蒽醌二蒽酮 A1 在 和 中都表现出不可阻挡的表型。
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