Synthesis and structure-activity relationships of hydroxylated and halogenated 2,4-diaryl benzofuro[3,2-b]pyridin-7-ols as selective topoisomerase IIα inhibitors

Bioorg Chem. 2021 Jun;111:104884. doi: 10.1016/j.bioorg.2021.104884. Epub 2021 Apr 1.


The objective of this study was to discover potential topoisomerase (topo) targeting anticancer agents. Novel series of hydroxylated and halogenated(-F, -Cl, and -CF3) 2,4-diaryl benzofuro[3,2-b]pyridin-7-ols were systematically designed and synthesized by faster, economic, and environmentally friendly l-proline catalyzed and microwave-assisted one pot reaction method. The synthesized compounds were assessed for topo I and IIα inhibitory and anti-proliferative activities. The in vitroevaluation displayed that most of the compounds have selective topo IIα inhibitoryactivity as well as selectivity towards T47D human cancer cell line. Structure-activity relationship study suggested that the introduction of additional hydroxyl functionality at 7-positon of benzofuro[3,2-b]pyridine skeleton is crucial for selective topo IIα inhibitory activity. Placement of phenolic moiety on the 4-position of the tricyclic system imparts better topo IIα inhibitory and anti-proliferative activity.

Keywords: Anti-proliferative activity; Benzofuro[3,2-b]pyridin-7-ol; Halogen moiety; Hydroxyl moiety; Structure-activity relationship; Topoisomerase inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzofurans / chemical synthesis
  • Benzofurans / chemistry
  • Benzofurans / pharmacology*
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type II / metabolism
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Halogenation
  • Humans
  • Hydroxylation
  • Molecular Structure
  • Poly-ADP-Ribose Binding Proteins / antagonists & inhibitors*
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors / chemical synthesis
  • Topoisomerase II Inhibitors / chemistry
  • Topoisomerase II Inhibitors / pharmacology*
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Benzofurans
  • Poly-ADP-Ribose Binding Proteins
  • Pyridines
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type II
  • TOP2A protein, human