Design, synthesis, and biological evaluation of 1,3,6,7-tetrahydroxyxanthone derivatives as phosphoglycerate mutase 1 inhibitors

Bioorg Med Chem Lett. 2021 Mar 15:36:127820. doi: 10.1016/j.bmcl.2021.127820. Epub 2021 Jan 26.

Abstract

Phosphoglycerate mutase 1 (PGAM1) is a promising target for cancer treatment. Herein, we found that α-mangostin and γ-mangostin exhibited moderate PGAM1 inhibitory activities, with IC50 of 7.2 μM and 1.2 µM, respectively. Based on α-mangostin, a series of 1,3,6,7-tetrahydroxyxanthone derivatives were designed, synthesized and evaluated in vitro for PGAM1 inhibition. The significant structure-activity relationships (SAR) and a fresh binding mode of this kind of new compounds were also clearly described. This study provides valuable information for further optimization of PGAM1 inhibitors with 1,3,6,7-tetrahydroxyxanthone backbone or de novo design of novel inhibitor.

Keywords: 1,3,6,7-Tetrahydroxyxanthone derivatives; Mangostin; PGAM1 inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Phosphoglycerate Mutase / antagonists & inhibitors*
  • Phosphoglycerate Mutase / metabolism
  • Structure-Activity Relationship
  • Xanthones / chemical synthesis
  • Xanthones / chemistry
  • Xanthones / pharmacology*

Substances

  • 1,3,6,7-tetrahydroxyxanthone
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Xanthones
  • Phosphoglycerate Mutase
  • phosphoglycerate mutase 1, human