Synthesis of 2-(thienyl-2-yl or -3-yl)-4-furyl-6-aryl pyridine derivatives and evaluation of their topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship

Bioorg Med Chem. 2010 Mar 15;18(6):2245-2254. doi: 10.1016/j.bmc.2010.01.065. Epub 2010 Feb 4.

Abstract

A series of 2-(thienyl-2-yl or -3-yl)-4-furyl-6-aryl pyridine derivatives were designed, synthesized, and evaluated for their topoisomerase I and II inhibition and cytotoxic activity against several human cancer cell lines. Compounds 10-19 showed moderate topoisomerase I and II inhibitory activity and 20-29 showed significant topoisomerase II inhibitory activity. Structure-activity relationship study revealed that 4-(5-chlorofuran-2-yl)-2-(thiophen-3-yl) moiety has an important role in displaying topoisomerase II inhibition.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type I / chemistry
  • DNA Topoisomerases, Type I / metabolism
  • DNA Topoisomerases, Type II / chemistry
  • DNA Topoisomerases, Type II / metabolism
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*
  • Topoisomerase II Inhibitors*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Pyridines
  • Topoisomerase I Inhibitors
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type I
  • DNA Topoisomerases, Type II
  • pyridine