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

Autor: Chen H; 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., Yang X; School of Pharmacy, Second Military Medical University, Shanghai 200433, China., Yu Z; School of Pharmacy, Second Military Medical University, Shanghai 200433, China., Cheng Z; School of Pharmacy, Second Military Medical University, Shanghai 200433, China., Yuan H; Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China., Zhao Z; 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., Wu G; School of Pharmacy, Second Military Medical University, Shanghai 200433, China., Xie N; State Key Laboratory of Innovative Natural Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd, Ganzhou 341000, Jiangxi, China., Yuan X; School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: yuanxing2012@126.com., Sun Q; Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China. Electronic address: sqy_2000@163.com., Zhang W; School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China. Electronic address: wdzhangy@hotmail.com.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2018 Apr 10; Vol. 149, pp. 90-97. Date of Electronic Publication: 2018 Feb 23.
DOI: 10.1016/j.ejmech.2018.02.073
Abstrakt: 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 IC 50 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.
(Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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