6,6’-Dihydroxythiobinupharidine as a poison of human type II topoisomerases

Esha D. Dalvie, Jacob Gopas, Avi Golan-Goldhirsh, Neil Osheroff

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


A number of natural products with medicinal properties increase DNA cleavage mediated by type II topoisomerases. In an effort to identify additional natural compounds that affect the activity of human type II topoisomerases, a blind screen of a library of 341 Mediterranean plant extracts was conducted. Extracts from Nuphar lutea, the yellow water lily, were identified in this screen. N. lutea has been used in traditional medicine by a variety of indigenous populations. The active compound in N. lutea, 6,6’-dihydroxythiobinupharidine, was found to enhance DNA cleavage mediated by human topoisomerase IIα and IIβ ∼8-fold and ∼3-fold, respectively. Mechanistic studies with topoisomerase IIα indicate that 6,6’-dihydroxythiobinupharidine is a “covalent poison” that acts by adducting the enzyme outside of the DNA cleavage-ligation active site and requires the N-terminal domain of the protein for its activity. Results suggest that some of the medicinal properties of N. lutea may result from the interactions between 6,6’-dihydroxythiobinupharidine and the human type II enzymes.

Original languageEnglish
Pages (from-to)1881-1885
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number15
StatePublished - 1 Aug 2019


  • 6,6’-Dihydroxythiobinupharidine
  • Covalent poison
  • DNA cleavage
  • Topoisomerase IIα
  • Topoisomerase IIβ

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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