Synthetic derivatives of the natural product 13-amino 2-desoxy-4-epi-pulchellin inhibit STAT3 signaling and induce G2/M arrest and death of colon cancer cells

Bioorg Med Chem Lett. 2019 Mar 15;29(6):782-785. doi: 10.1016/j.bmcl.2019.01.030. Epub 2019 Jan 25.

Abstract

2-Desoxy-4-epi-puchellin (PCL) is a sesquiterpene-lactone, which naturally occurs in many traditional Chinese medicinal plants, and has antitumor and anti-inflammatory activities. In this work, a series of 13-amino derivatives of PCL were synthesized through Michael addition reaction. Inhibition of IL-6-induced STAT3 signaling pathway and in vitro cytotoxicity of these compounds were evaluated, and their effect on the cell cycle was also studied. The methyl hydroxyethylamine derivatives showed higher potency than PCL, which could induce significant mitotic arrest via G2/M arrest in HCT116 cancer cells, indicating that these derivatives have the potential to be developed into anti-colon cancer drugs.

Keywords: Antitumor; Colorectal carcinoma; JAK2/STAT3; Michael addition reaction; Sesquiterpene-lactone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemical synthesis
  • Amines / chemistry
  • Amines / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • HCT116 Cells
  • Humans
  • Lactones / chemical synthesis
  • Lactones / chemistry
  • Lactones / pharmacology*
  • Molecular Structure
  • STAT3 Transcription Factor / metabolism
  • Sesquiterpenes / chemical synthesis
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects*
  • Structure-Activity Relationship

Substances

  • Amines
  • Antineoplastic Agents
  • Lactones
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Sesquiterpenes