Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity

J Med Chem. 2018 Feb 8;61(3):1375-1379. doi: 10.1021/acs.jmedchem.7b01388. Epub 2017 Nov 9.

Abstract

We used a pharmacophore hybridization strategy to combine key structural elements of merbarone and etoposide and generated new type II topoisomerase (topoII) poisons. This first set of hybrid topoII poisons shows promising antiproliferative activity on human cancer cells, endorsing their further exploration for anticancer drug discovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type II / chemistry
  • DNA Topoisomerases, Type II / metabolism*
  • Drug Design*
  • Humans
  • Molecular Docking Simulation
  • Protein Conformation
  • Topoisomerase II Inhibitors / chemistry*
  • Topoisomerase II Inhibitors / metabolism
  • Topoisomerase II Inhibitors / pharmacology*

Substances

  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type II