青蒿素类药物靶标及其免疫调节抗肿瘤机制研究进展

Research progresses on drug targets,immunomodulatory activity,and anti-tumor mechanisms of artemisinin and its analogues

青蒿素及其衍生物是一类含有过氧基团的倍半萜内酯药物,已经成为国际上广泛认可并使用的抗疟疾首选药物。青蒿素类药物需要经过血红素依赖或线粒体途径激活后,释放自由基来杀死疟原虫,但目前其激活的具体机制还不清楚。尽管青蒿素抗疟疾作用的靶标蛋白如翻译调控肿瘤蛋白、肌浆网/内质网钙转运ATP酶和磷脂酰肌醇-3-激酶已经研究的比较清楚,但新近发现的一些潜在作用靶点仍有待进一步阐明。青蒿素及其衍生物除了具有神奇的抗疟疾疗效外,近年来也发现具有免疫调节和抗肿瘤的作用。本文将对青蒿素及其衍生物激活方式、作用靶标以及免疫调节和抗肿瘤作用机制进行综述。

Artemisinin and its derivatives are a class bridge, which has been widely recognized and used in the world of sesquiterpene lactones containing endoperoxide as the first choice for anti-malaria drugs. Artemisinin drugs need to release free radicals to kill malaria parasites after activating by heme or mitochondrial dependent pathways, but the specific mechanisms of their activation remain unclear. Although many target proteins of anti- malaria artemisinins such as translational controlled tumor protein, sarcoplasmic reticulum/endoplasmic reticulum calcium transport ATPase and phosphatidylinositol-3-kinase have been studied clearly, novel target proteins have yet to be elucidated. Artemisinin and its derivatives have been found to have immunomodulatory and anti-tumor effects in addition to their magical anti-malarial efficacy. This article will review the activation modes of artemisinin and its derivatives, the targets of action and the mechanisms of immunomodulation and anti-tumor effects.