Nitro and amino substitution within the A-ring of 5H-8,9-dimethoxy-5-(2-N, N-dimethylaminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones

Influence on topoisomerase I-targeting activity and cytotoxicity

Alexander L. Ruchelman, John E. Kerrigan, Tsai Kun Li, Nai Zhou, Angela Liu, Leroy-Fong Liu, Edmond J. LaVoie

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Recently, 5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3- methylenedioxydibenzo[c,h][1,6]naphthyridin-6-one, 1, was identified as a TOP1-targeting agent with pronounced antitumor activity. In the present study, the effect on activity of substituting a single nitro or amino group in the A-ring in lieu of the methylenedioxy moiety of 1 was evaluated. The presence of either a nitro or amino substituent at the 4-position had a pronounced adverse affect on both TOP1-targeting activity and cytotoxicity. To a lesser extent, derivatives with a nitro or amino substituent at the 1-position were also less active than 1. Replacement of the methylenedioxy moiety of 1 with either a nitro or amino substituent at either the 2- and 3-position did result in analogues with potent TOP1-targeting activity and cytotoxicity.

Original languageEnglish
Pages (from-to)3731-3742
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number13
DOIs
Publication statusPublished - Jul 1 2004
Externally publishedYes

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Type I DNA Topoisomerase
Cytotoxicity
Substitution reactions
Derivatives

ASJC Scopus subject areas

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

Cite this

Nitro and amino substitution within the A-ring of 5H-8,9-dimethoxy-5-(2-N, N-dimethylaminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones : Influence on topoisomerase I-targeting activity and cytotoxicity. / Ruchelman, Alexander L.; Kerrigan, John E.; Li, Tsai Kun; Zhou, Nai; Liu, Angela; Liu, Leroy-Fong; LaVoie, Edmond J.

In: Bioorganic and Medicinal Chemistry, Vol. 12, No. 13, 01.07.2004, p. 3731-3742.

Research output: Contribution to journalArticle

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T2 - Influence on topoisomerase I-targeting activity and cytotoxicity

AU - Ruchelman, Alexander L.

AU - Kerrigan, John E.

AU - Li, Tsai Kun

AU - Zhou, Nai

AU - Liu, Angela

AU - Liu, Leroy-Fong

AU - LaVoie, Edmond J.

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