5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)dibenzo[c,h][1,6] naphthyridin-6-ones and related compounds as TOP1-targeting agents: Influence of structure on the ternary cleavable complex formation

John E. Kerrigan, Daniel S. Pilch, Alexander L. Ruchelman, Nai Zhou, Angela Liu, Leroy Liu, Edmond J. LaVoie

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

In this paper, we present our results from a docking study of the title compounds with the DNA/topoisomerase I complex based on the recently published X-ray crystal structure of the topotecan/DNA/topoisomerase I ternary cleavable complex (Staker, B.L., et al. PNAS 2002, 99, 15387) using the Autodock program. Simple intermolecular docking energies (Edock) correlate well with in vitro DNA cleavage data suggesting that the binding mode from the crystal structure is a reasonable binding mode for these compounds.

Original languageEnglish
Pages (from-to)3395-3399
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume13
Issue number20
DOIs
Publication statusPublished - Oct 20 2003
Externally publishedYes

ASJC Scopus subject areas

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

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