Achyrodimer F, a tyrosyl-DNA phosphodiesterase I inhibitor from an Australian fungus of the family Cortinariaceae

Bioorg Med Chem Lett. 2017 Sep 1;27(17):4007-4010. doi: 10.1016/j.bmcl.2017.07.062. Epub 2017 Jul 24.

Abstract

Mass-guided isolation of the dichloromethane/methanol extracts from a specimen of teleomorphic fungus of the family Cortinariaceae resulted in the identification of a new dimeric cyclobutane metabolite, achyrodimer F (1), along with the monomers hispidin (2) and bisnoryangonin (3). Their structures were determined by NMR and MS data analyses. Density Function Theory (DFT) NMR calculations was employed to confirm the chemical structure of achyrodimer F. Compound 1 inhibited tyrosyl-DNA phosphodiesterase I with an IC50 value of 1μM.

Keywords: Achyrodimer F; Cyclobutane derivative; DFT calculations; Fungus Cortinariaceae; Tdp1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / chemistry*
  • Australia
  • Cyclobutanes / chemistry
  • Cyclobutanes / isolation & purification
  • Cyclobutanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / isolation & purification
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases / metabolism*
  • Pyrones / chemistry
  • Pyrones / isolation & purification
  • Pyrones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Cyclobutanes
  • Phosphodiesterase Inhibitors
  • Pyrones
  • achyrodimer F
  • Phosphoric Diester Hydrolases
  • TDP1 protein, human