基于青蒿素的二聚体/杂合体的抗肿瘤活性

The Anticancer Potential of Artemisinin-based Dimers/hybrids

除经典的抗疟疾活性外,青蒿素类化合物还具有潜在的体内外抗肿瘤活性。研究表明,青蒿素母核中的倍半萜内酯结构片段可在肿瘤细胞血红素二价铁离子的作用下发生开环反应,产生能抑制肿瘤转移、肿瘤相关信号通路和血管生成的高活性自由基,促使肿瘤凋亡。青蒿素单核衍生物往往由于抗肿瘤活性较低等因素限制了这类化合物在抗肿瘤领域的应用,而青蒿素二聚体和杂合体则普遍具有更高的体内外抗肿瘤活性和良好的药代动力学性质,引起了药物化学家的极大兴趣。本文着重介绍了近五年来基于青蒿素母核的二聚体和杂合体在抗肿瘤领域的最新研究进展,以启迪药物化学家更合理的设计此类化合物。

Besides the classical antimalarial activity,artemisinin-based compounds also exhibit potential in vitro and in vivo anticancer activity.The peroxide-containing sesquiterpene lactone skeleton in artemisinin backbone could be cleaved in the presence of ferrous ion to generate highly reactive radicals which have the ability to inhibit metastasis,cancer-related signaling pathways,and angiogenesis,and consequently induce cancer cells death.The activity of artemisinin-based monomers is usually not enough to fight against cancer cells,whereas artemisinin-based dimers and hybrids not only exhibit enhanced in vitro and in vivo anticancer activity,but also possess excellent pharmacokinetic profiles,revealing their potential as putative anticancer agents.This review will provide an overview of artemisinin-based dimers and hybrids with potential therapeutic application for treatment of cancers development in recent 5 years.We hope this review could provide a guide to develop new anti-cancer agents with greater potency against drug-sensitive and drug-resistant cancers in the future.