6-Substituted 6H-dibenzo[c,h][2,6]naphthyridin-5-ones: Reversed lactam analogues of ARC-111 with potent topoisomerase I-targeting activity and cytotoxicity

Shejin Zhu, Alexander L. Ruchelman, Nai Zhou, Angela Liu, Leroy-Fong Liu, Edmond J. LaVoie

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22 Citations (Scopus)


6-Substituted 8,9-dimethoxy-2,3-methylenedioxy-6H-dibenzo[c,h][2,6] naphthyridin-5-ones were synthesized and evaluated for topoisomerase I-targeting activity and cytotoxicity. Several of these reversed lactam analogues of ARC-111 exhibited exceptional cytotoxicity with IC50 values ranging from 0.5 to 3.0 nM. In contrast to topotecan, no resistance was observed with several of these reversed lactam analogues in tumor cell lines that overexpressed the efflux transporters MDR1 or BCRP.

Original languageEnglish
Pages (from-to)3131-3143
Number of pages13
JournalBioorganic and Medicinal Chemistry
Issue number9
Publication statusPublished - May 1 2006
Externally publishedYes



  • Antitumor
  • Cytotoxic
  • Dibenzo[c,h][2,6]naphthyridin-5-ones
  • Topoisomerase I

ASJC Scopus subject areas

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

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