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  2. Study on the structure-activity relationship of dihydroartemisinin derivatives: Discovery, synthesis, and biological evaluation of dihydroartemisinin-bile acid conjugates as potential anticancer agents

Study on the structure-activity relationship of dihydroartemisinin derivatives: Discovery, synthesis, and biological evaluation of dihydroartemisinin-bile acid conjugates as potential anticancer agents

  • Eur J Med Chem. 2021 Dec 5:225:113754. doi: 10.1016/j.ejmech.2021.113754.
Xiaosu Zou 1 Chang Liu 2 Congcong Li 1 Rong Fu 3 Wei Xu 1 Hongzhu Bian 4 Xun Dong 4 Xiaozhen Zhao 2 Zhenye Xu 5 Jinghua Zhang 6 Zhengwu Shen 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 CaiLun Road, Shanghai, 201203, China.
  • 2 Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South WanPing Road, Shanghai, 200032, China.
  • 3 School of Medicine, Shanghai Jiao Tong University, 280 South Chongqing Road, Shanghai, 200025, China.
  • 4 Yunnan Baiyao Group Co. Ltd, 3686 Yunnan Baiyao Street, Kunming, 650200, China.
  • 5 Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South WanPing Road, Shanghai, 200032, China. Electronic address: xuzhenye1947@126.com.
  • 6 School of Medicine, Shanghai Jiao Tong University, 280 South Chongqing Road, Shanghai, 200025, China. Electronic address: 183930@shsmu.edu.cn.
  • 7 School of Medicine, Shanghai Jiao Tong University, 280 South Chongqing Road, Shanghai, 200025, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 CaiLun Road, Shanghai, 201203, China. Electronic address: Jeff_shen_1999@yahoo.com.
Abstract

A series of dihydroartemisinin derivatives was synthesized, and their anti-proliferation activity against Cancer cells was evaluated. Structure-activity relationship studies led to the discovery of dihydroartemisinin-bile acid conjugates that exhibit broad-spectrum anti-proliferation activities. Among them, the dihydroartemisinin-ursodeoxycholic acid conjugate (49) was the most potent, with IC50 values between 0.04 and 0.96 μM when tested to determine its inhibitory properties against 15 various Cancer cell lines. In vivo experiments showed that compound 49 effectively suppressed tumor growth in an A549 cell xenograft model at the dosage of 10 mg/kg body weight and in Lewis lung Cancer cell transplant model at the dosage of 12 mg/kg body weight.

Keywords

Anticancer agent; Artemisinin; Bile acid; Conjugates; Ursodeoxycholic acid.

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