Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
Bioorg Med Chem Lett. 2013 Aug 1;23(15):4424-7. doi: 10.1016/j.bmcl.2013.05.057. Epub 2013 May 28.
The Ugi four-component reaction was used to prepare a series of artemisinin monomers and dimers. We found that the endoperoxide group in artemisinin remains intact during the reaction. The new artemisinin dimers showed potent anti-cancer activity against two human breast cancer cell lines, MDA-MB-231 and BT-474. One of the Ugi artemisinin dimers showed an IC₅₀ value of 12 nM when tested on BT474 cells, more than 600 times more potent than artesunate. Furthermore, the same Ugi artemisinin dimer showed a low toxicity when tested on MCF10A, a nontumorigenic cell line, resulting in a selectivity index of more than 8000.
乌吉（Ugi）四组分反应被用于制备一系列青蒿素单体和二聚体。我们发现青蒿素分子中的过氧基团在反应过程中保持完整。新的青蒿素二聚体对两种人乳腺癌细胞系 MDA-MB-231 和 BT-474 表现出很强的抗癌活性。其中一个乌吉青蒿素二聚体在 BT474 细胞上的 IC₅₀ 值为 12 nM，比青蒿琥酯强 600 多倍。此外，相同的乌吉青蒿素二聚体在非致瘤细胞系 MCF10A 上表现出较低的毒性，选择性指数超过 8000。
