Isodiospyrin as a novel human DNA topoisomerase I inhibitor

Biochem Pharmacol. 2003 Nov 15;66(10):1981-91. doi: 10.1016/j.bcp.2003.07.003.


Isodiospyrin is a natural product from the plant Diospyros morrisiana, which consists of an asymmetrical 1,2-binaphthoquinone chromophore. Isodiospyrin exhibits cytotoxic activity to tumor cell lines but very little is known about its cellular target and mechanism of action. Unlike the prototypic human topoisomerase I (htopo I) poison camptothecin, isodiospyrin does not induce htopo I-DNA covalent complexes. However, isodiospyrin antagonizes camptothecin-induced, htopo I-mediated DNA cleavage. Binding analysis indicated that isodiospyrin binds htopo I but not DNA. These results suggest that isodiospyrin inhibits htopo I by direct binding to htopo I, which limits htopo I access to the DNA substrate. Furthermore, isodiospyrin exhibits strong inhibitory effect on the kinase activity of htopo I toward splicing factor 2/alternate splicing factor in the absence of DNA. Thus, these findings have important implications on naphthoquinone and its derivatives' cellular mode of actions, i.e. these novel DNA topoisomerase I inhibitors can prevent both DNA relaxation and kinase activities of htopo I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • DNA / drug effects
  • DNA / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Naphthoquinones / pharmacology*
  • Topoisomerase I Inhibitors*


  • Enzyme Inhibitors
  • Naphthoquinones
  • Topoisomerase I Inhibitors
  • isodiospyrin
  • Adenosine Triphosphate
  • DNA