2. Academic Validation
  3. Synthesis of artemisinin-piperazine-furan ether hybrids and evaluation of in vitro cytotoxic activity

Synthesis of artemisinin-piperazine-furan ether hybrids and evaluation of in vitro cytotoxic activity

  • Eur J Med Chem. 2021 Apr 5:215:113295. doi: 10.1016/j.ejmech.2021.113295.
Meng-Xue Wei 1,  Jia-Ying Yu 2,  Xin-Xin Liu 2,  Xue-Qiang Li 2,  Meng-Wei Zhang 2,  Pei-Wen Yang 2,  Jin-Hui Yang 2
Affiliations

Affiliations

  • 1 State Key Laboratory of High-efficiency Utilization of Coal and Green Chemical Engineering, Ningxia Engineering Research Center for Natural Medicine, National Demonstration Center for Experimental Chemistry Education, College of Chemistry and Chemical Engineering, Ningxia University, 489 Helanshan West Road, Yinchuan, 750021, China. Electronic address: weimengxue@nxu.edu.cn.
  • 2 State Key Laboratory of High-efficiency Utilization of Coal and Green Chemical Engineering, Ningxia Engineering Research Center for Natural Medicine, National Demonstration Center for Experimental Chemistry Education, College of Chemistry and Chemical Engineering, Ningxia University, 489 Helanshan West Road, Yinchuan, 750021, China.
PMID: 33636536 DOI: 10.1016/j.ejmech.2021.113295
Abstract

For the first time, eight novel artemisinin-piperazine-furane ether hybrids (5a-h) were efficiently synthesized and investigated for their in vitro cytotoxic activity against some human Cancer and benign cells. The absolute configuration of hybrid 5c was determined by X-ray crystallographic analysis. Hybrids 5a-h exhibited more pronounced growth-inhibiting action on hepatocarcinoma cell lines than their parent dihydroartemisinin (DHA) and the reference cytosine arabinoside (ARA). The hybrid 5a showed the best cytotoxic activity against human hepatocarcinoma cells SMMC-7721 (IC50 = 0.26 ± 0.03 μM) after 24 h. Furthermore, hybrid 5a also showed good cytotoxic activity against human breast Cancer cells MCF-7 and low cytotoxicity against human breast benign cells MCF-10A in vitro. We found the cytotoxicity of hybrid 5a did not change when tumour cells absorb iron sulfate (FeSO4); thus, we conclude the anti-tumour mechanism induced by iron ions (Fe2+) is unclear.

Keywords

Artemisinin; Cancer cells; Cytotoxic activity; Furan ether; X-ray crystallography.

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