新型线粒体靶向青蒿素酯衍生物的合成与生物活性。
Synthesis and biological activities of novel mitochondria-targeted artemisinin ester derivatives.
机构信息
Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China.
Department of Laboratory Medicine, School of Medicine, Hunan Normal University, Changsha, Hunan, China.
出版信息
Bioorg Med Chem Lett. 2021 May 1;39:127912. doi: 10.1016/j.bmcl.2021.127912. Epub 2021 Mar 7.
A series of novel artemisinin ester derivatives were designed and synthesized for targeting mitochondria. Cytotoxicity against SMMC-7721, HepG2, OVCAR3, A549 and J82 cancer cell lines was evaluated. Compound 2c (IC = 3.0 μM) was the most potent anti-proliferative molecule against the OVCAR3 cells with low cytotoxicity in normal HUVEC cells. The mechanism of action of compound 2c was further investigated by analyzing cell apoptosis, mitochondrial membrane potential (Δψm) and intracellular ROS generation. The results indicated that compound 2c targeted mitochondria and induced cell apoptosis. ROS and heme attributed to the cytotoxicity and cell apoptosis of compound 2c. These promising findings indicated the compound 2c could serve as a great candidate against ovarian cancer for further investigation.
设计并合成了一系列新型青蒿素酯衍生物，以靶向线粒体。评估了它们对 SMMC-7721、HepG2、OVCAR3、A549 和 J82 癌细胞系的细胞毒性。化合物 2c（IC=3.0 μM）对 OVCAR3 细胞具有最强的增殖抑制活性，而对正常 HUVEC 细胞的细胞毒性较低。通过分析细胞凋亡、线粒体膜电位（Δψm）和细胞内 ROS 生成，进一步研究了化合物 2c 的作用机制。结果表明，化合物 2c 靶向线粒体并诱导细胞凋亡。ROS 和血红素是化合物 2c 产生细胞毒性和诱导细胞凋亡的原因。这些有前景的发现表明，化合物 2c 可能成为进一步研究卵巢癌的一个很好的候选药物。
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