State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Molecules. 2010 Mar 8;15(3):1378-97. doi: 10.3390/molecules15031378.
Artemisinins have become essential antimalarial drugs for increasingly widespread drug-resistant malaria strains. Although tremendous efforts have been devoted to decipher how this class of molecules works, their exact antimalarial mechanism is still an enigma. Several hypotheses have been proposed to explain their actions, including alkylation of heme by carbon-centered free radicals, interference with proteins such as the sarcoplasmic/endoplasmic calcium ATPase (SERCA), as well as damaging of normal mitochondrial functions. Besides artemisinins, other endoperoxides with various backbones have also been synthesized, some of which showed comparable or even higher antimalarial effects. It is noteworthy that among these artemisinin derivatives, some enantiomers displayed similar in vitro malaria killing efficacy. In this article, the proposed mechanisms of action of artemisinins are reviewed in light of medicinal chemistry findings characterized by efficacy-structure studies, with the hope of gaining more insight into how these potent drugs work.
青蒿素已成为治疗耐药疟原虫感染的重要抗疟药物。尽管人们已经做出了巨大的努力来阐明这类分子的作用机制，但它们的确切抗疟机制仍然是一个谜。已经提出了几种假说来解释它们的作用，包括碳中心自由基对血红素的烷基化、干扰肌浆/内质网钙 ATP 酶 (SERCA) 等蛋白质，以及破坏正常的线粒体功能。除了青蒿素，还合成了具有各种骨架的其他过氧化物，其中一些表现出相当或更高的抗疟效果。值得注意的是，在这些青蒿素衍生物中，一些对映异构体显示出类似的体外疟原虫杀伤效果。在本文中，根据以药效-结构研究为特征的药物化学发现，综述了青蒿素的作用机制，希望能更深入地了解这些强效药物的作用方式。
