Synthesis and biological evaluation of α-santonin derivatives as anti-hepatoma agents

  • Eur J Med Chem. 2018 Apr 10:149:90-97. doi: 10.1016/j.ejmech.2018.02.073.
Hao Chen  1 ,  Xiao Yang  2 ,  Zongmin Yu  2 ,  Ziying Cheng  2 ,  Hu Yuan  3 ,  Zeng Zhao  1 ,  Guozhen Wu  2 ,  Ning Xie  4 ,  Xing Yuan  5 ,  Qingyan Sun  6 ,  Weidong Zhang  7
Affiliations
  • 1. School of Pharmacy, Second Military Medical University, Shanghai 200433, China; State Key Laboratory of Innovative Natural Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd, Ganzhou 341000, Jiangxi, China.
  • 2. School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
  • 3. Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China.
  • 4. State Key Laboratory of Innovative Natural Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd, Ganzhou 341000, Jiangxi, China.
  • 5. School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: [email protected].
  • 6. Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China. Electronic address: [email protected].
  • 7. School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China. Electronic address: [email protected].
PMID: 29499490 DOI: 10.1016/j.ejmech.2018.02.073
Abstract

A series of α-santonin-derived compounds as potentially anti-hepatoma agents were designed and synthesized in an effort to find novel therapeutic agents. Among them, derivative 5h was more potent than the positive control 5-fluorouracil (5-Fu) on HepG-2, QGY-7703 and SMMC-7721 with IC50 values of 7.51, 3.06 and 4.08 μM, respectively. The structure-activity relationships (SARs) of these derivatives were discussed. In addition, flow cytometry and western blot assay revealed that the derivatives induced hepatoma cells Apoptosis by facilitating apoptosis-related proteins expressions. Our findings suggested that these α-santonin-derived analogues hold promise as chemotherapeutic agents for the treatment of human hepatocellular Cancer.

Keywords
Anti-hepatoma; Apoptotic; Structure-activity relationships; α-Methylene-γ-lactone; α-Santonin-derived analogues.