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.
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: [email protected].
- 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: [email protected].
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.