2. Academic Validation
  3. Discovery and synthesis of novel Wogonin derivatives with potent antitumor activity in vitro

Discovery and synthesis of novel Wogonin derivatives with potent antitumor activity in vitro

  • Eur J Med Chem. 2017 Nov 10:140:421-434. doi: 10.1016/j.ejmech.2017.09.046.
Jubo Wang 1,  Raoling Ge 1,  Xiaqiu Qiu 1,  Xi Xu 1,  Libin Wei 2,  Zhiyu Li 3,  Jinlei Bian 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Design and Optimization, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
  • 2 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Basic Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
  • 3 Jiangsu Key Laboratory of Drug Design and Optimization, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address: zhiyuli@cpu.edu.cn.
  • 4 Jiangsu Key Laboratory of Drug Design and Optimization, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address: bianjl@cpu.edu.cn.
PMID: 28987604 DOI: 10.1016/j.ejmech.2017.09.046
Abstract

Phenotypic screening of high quality compound library is one of the most effective strategy to obtain novel bioactive compounds. Recently, our group have constructed a Wogonin-scaffold library with substituents diversity and successfully obtained a series of potent compounds. Herein, we reported the synthesis of these compounds and evaluated the in vitro antitumor activity against a panel of human tumor cell lines. Most of them showed good activity with a broad spectrum and preliminary structure-activity relationship for the substitutions were obtained. Further biological assays showed that the most potent compounds 18n and 20b could significantly enhance the intracellular ROS level and induce the cell Apoptosis at low micromole level. Through similarity searching, CDK9 was identified as the potential target for 20b, which could be a start point for next structure-based drug design.

Keywords

Antitumor; Phenotypic screening; ROS; Target fishing; Wogonin.

Figures