青蒿素
双氢青蒿素
化学
细胞毒性
哌嗪
效力
噻唑
部分
IC50型
细胞凋亡
细胞毒性T细胞
立体化学
生物化学
药理学
组合化学
体外
生物
恶性疟原虫
有机化学
免疫学
疟疾
作者
Meng‐Xue Wei,Si-Si Zhang,Xuanrong Sun,Zhihao Liu,Pei-Wen Yang,Xueqiang Li
出处
期刊:ChemMedChem
[Wiley]
日期:2022-07-13
卷期号:17 (17)
被引量:1
标识
DOI:10.1002/cmdc.202200239
摘要
A series of novel artemisinin-piperazine-phosphoramide mustard (PPM) hybrids were designed and synthesized by incorporating phosphoramide mustard (PM) into dihydroartemisinin (DHA) via an efficient, catalyst-free two-step sequential substitution. Artemisinin-PPM hybrids showed better cytotoxic potency against HepG2 cells than both the parent DHA and the reference, vincristine (VCR). Structure-activity relationship (SAR) studies showed that the cytotoxicity was significantly enhanced by the introduction of a thiazole moiety. Hybrid 7 h, the most potent compound with the highest selectivity index IC50 (HEK-293T)/IC50 (HepG2)=16, displayed 7.4-fold stronger potency than VCR against HepG2 cells. In addition, hybrid 7 h was substantially more cytotoxic on all human cancer cells tested than on the corresponding non-cancerous cells. Flow cytometric analysis showed that 7 h significantly blocked the cell cycle in the G0/G1 phase and induced apoptosis in a concentration-dependent manner.
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