2. Academic Validation
  3. Novel dissymmetric 3,5-bis(arylidene)-4-piperidones as potential antitumor agents with biological evaluation in vitro and in vivo

Novel dissymmetric 3,5-bis(arylidene)-4-piperidones as potential antitumor agents with biological evaluation in vitro and in vivo

  • Eur J Med Chem. 2018 Mar 10:147:21-33. doi: 10.1016/j.ejmech.2018.01.088.
Ning Li 1,  Wen-Yu Xin 1,  Bin-Rong Yao 1,  Chun-Hua Wang 1,  Wei Cong 1,  Feng Zhao 1,  Hong-Juan Li 1,  Yun Hou 1,  Qing-Guo Meng 2,  Gui-Ge Hou 3
Affiliations

Affiliations

  • 1 School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, PR China.
  • 2 School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, People's Republic of China. Electronic address: qinggmeng@163.com.
  • 3 School of Pharmacy, The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, PR China. Electronic address: guigehou@163.com.
PMID: 29421568 DOI: 10.1016/j.ejmech.2018.01.088
Abstract

Thirty-five novel dissymmetric 3,5-bis(arylidene)-4-piperidone derivatives (BAPs, 6a-h, 7a-h, 8a-g, 9a-g, 10a-e) were synthesized and evaluated the cytotoxicity. BAPs 6d, 7h, 8g, 9g demonstrated the most potentially inhibitory activities against HepG2 and THP-1 but lower cytotoxicity toward LO2. In vitro, 6d, 7h, 8g, 9g can effectively up-regulate Bax expression, down-regulate Bcl-2 expression in HepG2 cell. They could reasonably bind to the active site of Bcl-2 protein proved by molecular docking modes. The most active BAP 6d induced HepG2 cells Apoptosis in a dose-dependent manner by flow cytometrey. The cellular uptake of HepG2 cells showed 6d mainly accumulated into the nuclei by confocal laser scanning microscopy (CLSM). In vivo, 6d suppressed the growth of HepG2 xenografts in nude mice and relatively nontoxic to mice. These results suggest that 6d could be therapeutically beneficial as potential therapeutic agent for the early clinical treatment of liver cancers.

Keywords

3,5-bis(arylidene)-4-piperidone; Cellular uptake; Cytotoxicity; Molecular docking; Tumor xenograft.

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