Discovery of novel jaspine B analogues as autophagy inducer. Issue 3 (1st February 2018)

• Record Type: Journal Article
• Authors: Zhang, En; Wang, Shang; Li, Li-Li; Hua, Yong-Gang; Yue, Jing-Fei; Li, Jin-Feng; Jin, Cheng-Yun
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 3(2018)
• Page Start: 497
• Page End: 502
• Publication Date: 2018-02-01
• Subjects: Jaspine B -- Pachastrissamine -- Anti-tumor -- Anti-proliferative -- Autophagy; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.12.011
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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. Compound7f showed the best overall cytotoxicity on PC-3 cells (IC50 = 0.85 μM). Further mechanistic studies revealed that compound7f 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.