Design, synthesis and antitumor activity of non-camptothecin topoisomerase I inhibitors

Bioorg Med Chem Lett. 2015 Oct 15;25(20):4693-6. doi: 10.1016/j.bmcl.2015.06.042. Epub 2015 Jun 26.

Abstract

Three groups of non-camptothecin compounds with four to five fused rings have been designed and synthesized. Their in vitro anti-proliferative activity has been evaluated with five different cancer cell lines (HCT116, PC3, U87MG, HepG2, SK-OV-3). Compounds B-2 and B-3 showed the most potent cell growth inhibition with IC50 of 169 nM and 325 nM against U87MG cell line correspondingly.

Keywords: Anti-cancer; Inhibitor; Synthesis; Topo I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Camptothecin
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type I / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Naphthalimides / chemical synthesis
  • Naphthalimides / chemistry
  • Naphthalimides / pharmacology*
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors / chemical synthesis
  • Topoisomerase I Inhibitors / chemistry
  • Topoisomerase I Inhibitors / pharmacology*

Substances

  • Antineoplastic Agents
  • Naphthalimides
  • Topoisomerase I Inhibitors
  • DNA Topoisomerases, Type I
  • Camptothecin