青蒿素-吲哚和青蒿素-咪唑杂合体的合成、细胞毒性评价及对 MCF-7/ADR 细胞多药耐药的逆转作用。
Artemisinin-indole and artemisinin-imidazole hybrids: Synthesis, cytotoxic evaluation and reversal effects on multidrug resistance in MCF-7/ADR cells.
机构信息
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
出版信息
Bioorg Med Chem Lett. 2019 May 1;29(9):1138-1142. doi: 10.1016/j.bmcl.2019.02.021. Epub 2019 Feb 20.
A series of artemisinin derivatives with MDR reversal activity were designed and synthesized. All hybrids were screened to anticancer activities against four human cancer cell lines (A549, MCF-7, HepG-2, MDA-MB-231) and normal human hepatic cell (L02) in vitro. Most of the new compounds showed higher anticancer activities than artemisinin, among which compounds 11a and 11c displayed superior potency with IC 6.78 μM and 5.25 μM against MCF-7, respectively. The further research indicated that the most potent 11c induced cell cycle arrest at G2 phase in MCF-7. Additionally, compound 11c showed remarkable MDR reversal activity which reversed adriamycin against MCF-7/ADR cells with IC 0.76 μM.
设计并合成了一系列具有多药耐药（MDR）逆转活性的青蒿素衍生物。所有的杂合分子都在体外针对四种人癌细胞系（A549、MCF-7、HepG-2、MDA-MB-231）和正常人类肝细胞（L02）进行了抗癌活性筛选。大多数新化合物的抗癌活性均高于青蒿素，其中化合物 11a 和 11c 对 MCF-7 的抑制活性最强，IC 6.78 μM 和 5.25 μM。进一步的研究表明，最强效的化合物 11c 诱导 MCF-7 细胞周期停滞在 G2 期。此外，化合物 11c 表现出显著的 MDR 逆转活性，逆转阿霉素对 MCF-7/ADR 细胞的作用，IC 0.76 μM。
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