2. Academic Validation
  3. Synthesis and biological evaluation of α-santonin derivatives as anti-hepatoma agents

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

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: yuanxing2012@126.com.
  • 6 Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China. Electronic address: sqy_2000@163.com.
  • 7 School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China. Electronic address: wdzhangy@hotmail.com.
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.

Figures