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

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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
Volume14
Issue number9
DOIs
Publication statusPublished - May 1 2006
Externally publishedYes

Fingerprint

Lactams
Type I DNA Topoisomerase
Cytotoxicity
Topotecan
Tumor Cell Line
Inhibitory Concentration 50
Tumors
Cells
topovale

Keywords

  • 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

Cite this

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

In: Bioorganic and Medicinal Chemistry, Vol. 14, No. 9, 01.05.2006, p. 3131-3143.

Research output: Contribution to journalArticle

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