2. Academic Validation
  3. Synthesis and biological evaluation of novel Jiyuan Oridonin A-1,2,3-triazole-azole derivatives as antiproliferative agents

Synthesis and biological evaluation of novel Jiyuan Oridonin A-1,2,3-triazole-azole derivatives as antiproliferative agents

  • Eur J Med Chem. 2018 Sep 5:157:1249-1263. doi: 10.1016/j.ejmech.2018.08.056.
Yu Ke 1,  Jian-Jia Liang 1,  Rui-Juan Hou 2,  Ming-Ming Li 1,  Long-Fei Zhao 1,  Wang Wang 1,  Ying Liu 1,  Hang Xie 1,  Rui-Hua Yang 1,  Tian-Xing Hu 1,  Jin-Yi Wang 1,  Hong-Min Liu 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Institute of Drug Discovery and Development, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, 450001, PR China.
  • 2 Henan Provincial People's Hospital, Henan Province, Zhengzhou, 450003, PR China.
  • 3 School of Pharmaceutical Sciences, Institute of Drug Discovery and Development, Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, 450001, PR China. Electronic address: [email protected].
PMID: 30193221 DOI: 10.1016/j.ejmech.2018.08.056
Abstract

As a continuation of our research on developing potent and potentially safe anti-proliferative agents, two series of novel Jiyuan Oridonin A-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their anti-proliferative activity against four selected Cancer cell lines (MGC-803, MCF-7, PC-3, Eca-109). Some compounds with better growth inhibitory effects were chosen to carry out further studies in A549 and SMMC-7721. Most of the synthesized compounds exhibited moderate to good activity against all the Cancer cell lines selected. Particularly, the most active agent 8b showed high potency against human Cancer cells with IC50 ranging from 0.2 ± 0.0 to 5.0 ± 0.9 μM. Cellular mechanism studies elucidated compound 8b arrests cell cycle at G1 phase and induce a strong apoptotic response in SMMC-7721 cells. Furthermore, 8b could inhibit the colony formation and migration via Wnt signaling pathway in SMMC-7721 cells. For all these reasons, compound 8b holds promising potential as anti-proliferative agent.

Keywords

1,2,3-Triazole-azole; Apoptosis; Ent-kaurene diterpenoid; Wnt signaling pathway.

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