Design, synthesis and biological evaluation of novel glycosylated diphyllin derivatives as topoisomerase II inhibitors

Eur J Med Chem. 2012 Jan;47(1):424-31. doi: 10.1016/j.ejmech.2011.11.011. Epub 2011 Nov 13.

Abstract

Recently, a novel glycosylated diphyllin derivative 11 which exhibiting potent anticancer activity by targeting topoisomerase IIα was reported by our group. In order to provide more molecules for structure-activity relationship (SAR) studies, 12 new glycosylated diphyllin analogs have been designed, synthesized, and evaluated for their biological activities. The SAR analysis revealed that (i) the sugar moiety on the diphyllin is essential for the anticancer activity; (ii) equatorial C4'-OH on the sugar is superior to the axial one, and (iii) a proper cyclic lipophilic group at the C4' and C6' of sugar might enhance the anticancer activity.

MeSH terms

  • Apoptosis / drug effects
  • Benzodioxoles
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • DNA Fragmentation / drug effects
  • DNA Topoisomerases, Type II / metabolism*
  • Dioxolanes / chemical synthesis
  • Dioxolanes / chemistry*
  • Dioxolanes / pharmacology*
  • Drug Design*
  • Drug Resistance, Multiple / drug effects
  • Glycosylation
  • Humans
  • Lignans / chemical synthesis
  • Lignans / chemistry*
  • Lignans / pharmacology*
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors / chemical synthesis
  • Topoisomerase II Inhibitors / chemistry*
  • Topoisomerase II Inhibitors / pharmacology*

Substances

  • Benzodioxoles
  • Dioxolanes
  • Lignans
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type II
  • diphyllin