Synthesis and Topoisomerase I inhibitory properties of klavuzon derivatives

Bioorg Chem. 2017 Apr;71:275-284. doi: 10.1016/j.bioorg.2017.02.012. Epub 2017 Feb 21.


Klavuzon is a naphthalen-1-yl substituted α,β-unsaturated δ-lactone derivative, and is one of the anti-proliferative members of this class of compounds. Asymmetric and racemic syntheses of novel α,β-unsaturated δ-lactone derivatives are important to investigate their potential for the treatment of cancer. In this study, asymmetric and racemic syntheses of heteroatom-substituted klavuzon derivatives are reported. The syntheses were completed by a well-known three-step procedure. Anti-proliferative activity of seven novel racemic klavuzon derivatives were reported against MCF-7, PC3, HCT116 p53+/+ and HCT116 p53-/- cancer cell lines. Topoisomerase I inhibitory properties of 5,6-dihydro-2H-pyran-2-one derivatives were also studied.

Keywords: Anti-proliferative activity; Klavuzon; Topoisomerase I inhibition; α,β-Unsaturated δ-lactone.

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
  • DNA Topoisomerases, Type I / metabolism*
  • Humans
  • Lactones / chemical synthesis
  • Lactones / chemistry*
  • Lactones / pharmacology*
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors / chemical synthesis
  • Topoisomerase I Inhibitors / chemistry*
  • Topoisomerase I Inhibitors / pharmacology*


  • Antineoplastic Agents
  • Lactones
  • Topoisomerase I Inhibitors
  • DNA Topoisomerases, Type I