Separation of Cdc25 dual specificity phosphatase inhibition and DNA cleaving activities in a focused library of analogs of the antitumor antibiotic Dnacin

Peter Wipf, Corey R. Hopkins, Eleanor O. Phillips, John S. Lazo

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Biological evaluation of 96 analogs and synthetic intermediates of the naphthyridinomycin-type antitumor antibiotic Dnacin led to the identification of several low-micromolar inhibitors of dual specificity phosphatases, specifically Cdc25A1, Cdc25B2, and VHR, as well as the tyrosine phosphatase PTP1B. While the parent Dnacins are potent DNA cleavage agents, most of the analog structures, even those that retained significant phosphatase inhibitory activities, did not lead to plasmid DNA cleavage. Thus, the DNA-targeting and the phosphatase-inhibitory activities of Dnacins can be assigned to different pharmacophores.

Original languageEnglish (US)
Pages (from-to)6367-6372
Number of pages6
JournalTetrahedron
Volume58
Issue number32
DOIs
Publication statusPublished - Aug 5 2002

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Keywords

  • Cdc25
  • DNA cleavage
  • Dnacin
  • Dual specificity phosphatase inhibitors
  • Natural product library
  • PTP1B
  • SAR
  • Tyrosine phosphatase
  • VHR

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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