Synthesis and biological evaluation of 20-epi-amino-20-deoxysalinomycin derivatives

  • Eur J Med Chem. 2018 Mar 25:148:279-290. doi: 10.1016/j.ejmech.2018.02.004.
Yu Li  1 ,  Qiuyan Shi  1 ,  Jiajia Shao  2 ,  Yaping Yuan  3 ,  Zhigang Yang  1 ,  Shizhen Chen  3 ,  Xin Zhou  3 ,  Shijun Wen  2 ,  Zhong-Xing Jiang  4
Affiliations
  • 1. Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China.
  • 2. State Key Laboratory of Oncology in South China, Sun-Yat-sen University Cancer Center, Sun-Yat-sen University, Guangzhou, 510060, China.
  • 3. State Key Laboratory for Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, China.
  • 4. Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China. Electronic address: [email protected].
PMID: 29466777 DOI: 10.1016/j.ejmech.2018.02.004
Abstract

To improve the druggability of salinomycin, a 20-epi-amino-20-deoxysalinomycin derivatives library was synthesized with high efficacy from which a few salinomycin derivatives with high potency and selectivity were identified through comprehensive cytotoxicity assay, including a fluorine-19 magnetic resonance sensitive tool molecule. Using a K-Ras cellular model, salinomycin and its derivatives showed different molecular mode of action from literature reports. These results would be valuable for developing salinomycin-based Cancer therapy.

Keywords
(19)F MRI; Anti-cancer drugs; K-ras pathway; Nature product modification; Salinomycin; Staudinger reaction.