2. Academic Validation
  3. Synthesis and biological activities of novel mitochondria-targeted artemisinin ester derivatives

Synthesis and biological activities of novel mitochondria-targeted artemisinin ester derivatives

  • Bioorg Med Chem Lett. 2021 May 1:39:127912. doi: 10.1016/j.bmcl.2021.127912.
Cangcang Xu 1,  Linfan Xiao 1,  Xia Zhang 2,  Tao Zhuang 3,  Lingli Mu 4,  Xiaoping Yang 5
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Laboratory Medicine, School of Medicine, Hunan Normal University, Changsha, Hunan, China.
  • 3 Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 4 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. Electronic address: moulingli@sina.com.
  • 5 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. Electronic address: Xiaoping.Yang@hunnu.edu.cn.
PMID: 33691167 DOI: 10.1016/j.bmcl.2021.127912
Abstract

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 (IC50 = 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.

Keywords

Antitumor; Apoptosis; Novel artemisinin ester derivatives; ROS; Δψm.

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