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. Epub 2017 Dec 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemical synthesis
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Molecular Structure
  • Sphingosine / analogs & derivatives*
  • Sphingosine / chemical synthesis
  • Sphingosine / chemistry
  • Sphingosine / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • pachastrissamine
  • Sphingosine