STAT3 inhibitory activity of naphthoquinones isolated from Tabebuia avellanedae

Bioorg Med Chem. 2020 Mar 15;28(6):115347. doi: 10.1016/j.bmc.2020.115347. Epub 2020 Jan 28.

Abstract

The extract of Tabebuia avellanedae has been used as a folk medicine, and the various biological activities of T. avellanedae have been extensively studied. However, few studies have reported which natural products play a role in their biological effects. In this study, we evaluated representative naphthoquinones isolated from T. avellanedae and found that furanonaphthoquinones were the key structures required to exhibit STAT3 phosphorylation inhibitory activities. Our SAR analysis indicated that removal of a hydroxyl group enhanced the STAT3 phosphorylation inhibitory activity. In addition, the combined results of a mobility shift assay, SH2 domain binding assay, and docking simulation by Autodock 4.2.6 suggested that (S)-5-hydroxy-2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione (1) could directly bind to the hinge region of STAT3.

Keywords: BBI 608; Furanonaphthoquinones; JAK-STAT pathway; STAT3 phosphorylation; Tabebuia avellanedae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Naphthoquinones / chemistry
  • Naphthoquinones / isolation & purification
  • Naphthoquinones / pharmacology*
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism
  • Structure-Activity Relationship
  • Tabebuia / chemistry*

Substances

  • Naphthoquinones
  • STAT3 Transcription Factor
  • STAT3 protein, human