青蒿素类药物的作用机制:一个长久未决的基础研究挑战

青蒿素是中国自主研制的抗疟良药,高效、低毒,许多基于青蒿素研发的衍生物具有良好的抗疟效果,近年来已成为抗疟的一线药物,受到世界医疗卫生界的充分肯定.虽然青蒿素结构奇特,抑疟效果显著,但40年来其生物作用机制之谜一直未被彻底破解.针对青蒿素类药物的作用机制,提出了不同的假说,如血红素参与青蒿素的激活并被烷基化从而起到抑疟作用,线粒体参与青蒿素的激活和作用过程,某些特定的蛋白是青蒿素作用靶点等.除抑疟外,青蒿素类药物在杀灭其他种类寄生虫、抑制某些癌症细胞以及抗病毒、治疗类风湿等方面也有一定作用.本文将对青蒿素类药物作用机制的研究进行综述及展望,包括抗疟疾过程中的药物激活、作用靶点以及简要的青蒿素抑制肿瘤细胞作用机制,以期为今后的研究提供帮助.

Mechanism of Action of Artemisinins:a Long Unsettled Challenge

Artemisinin,discovered by Chinese scientists in the early 1970s,is an effective antimalarial drug with low toxicity.Artemisinins(artemisinin and its derivatives) remain as the gold standard in combating ever increasing drug-resistant malaria.Although intensive efforts have been devoted to explore the mode of action of this class of drugs,its exact mechanism remains an enigma.Many hypotheses have been proposed,such as iron and heme model,mitochondria model,PfATP6 model,and so forth.Recent studies have demonstrated that artemisinin and its analogs also possess potent inhibitory activities on some other parasites,cancer,virus and rheumatism.The aim of this review is to provide a mechanistic overview of the action of artemisinins.