2. Academic Validation
  3. Discovery of novel jaspine B analogues as autophagy inducer

Discovery of novel jaspine B analogues as autophagy inducer

  • Bioorg Med Chem Lett. 2018 Feb 1;28(3):497-502. doi: 10.1016/j.bmcl.2017.12.011.
En Zhang 1,  Shang Wang 2,  Li-Li Li 2,  Yong-Gang Hua 2,  Jing-Fei Yue 2,  Jin-Feng Li 3,  Cheng-Yun Jin 4
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. Electronic address: zhangen@zzu.edu.cn.
  • 2 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.
  • 3 Kidney Transplantation, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450001, PR China.
  • 4 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: cyjin@zzu.edu.cn.
PMID: 29254641 DOI: 10.1016/j.bmcl.2017.12.011
Abstract

A series of 2-alkylaminomethyl jaspine B analogues were synthesized and evaluated for their cytotoxic effects on human lung adenocarcinoma, breast Cancer, and prostate Cancer cell lines and a mouse melanoma cell line. Most of the compounds exhibited moderate to good activity against the Cancer cell lines. Compound 7f showed the best overall cytotoxicity on PC-3 cells (IC50 = 0.85 μM). Further mechanistic studies revealed that compound 7f induced marked changes in PC-3 cell morphology, disrupted the mitochondrial membrane potential, and increased expression of the Autophagy proteins beclin-1, LC3, and p62.

Keywords

Anti-proliferative; Anti-tumor; Autophagy; Jaspine B; Pachastrissamine.

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