Nitro and amino substitution in the D-ring of 5-(2-dimethylaminoethyl)2,3-methylenedioxy-5H-dibenzo[c,h][1,6] naphthyridin-6-ones

Effect on topoisomerase-I targeting activity and cytotoxicity

Sudhir K. Singh, Alexander L. Ruchelman, Tsai Kun Li, Angela Liu, Leroy-Fong Liu, Edmond J. LaVoie

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

5H-8,9 -Dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxydibenzo [c,h][1,6]naphthyridin-6-one exhibits potent TOP1-targeting activity and pronounced antitumor activity. It was hypothesized that replacement of the two methoxyl groups with a nitro substituent would allow for retention of similar activity. In this study 8-, 9-, and 10-nitro-5H-2,3-methylenedioxy5-(2-N,N-dimethylaminoethyl)dibenzo[c,h][1,6] naphthyridin-6-one and their amino derivatives were synthesized and assessed for their relative TOP1-targeting activity and cytotoxicity. In the case of both the 8- and 9-nitro analogues, their TOP1-targeting activity and cytotoxicity are greater than that of camptothecin and comparable to that of 5H-8,9-dimethoxy-5-(2-N,Ndimethylaminoethyl)-2,3-methylenedioxydibenzo[c,h] [1,6]naphthyridin-6-one.

Original languageEnglish
Pages (from-to)2254-2257
Number of pages4
JournalJournal of Medicinal Chemistry
Volume46
Issue number11
DOIs
Publication statusPublished - May 22 2003
Externally publishedYes

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Camptothecin
Type I DNA Topoisomerase
Cytotoxicity
Substitution reactions
Derivatives

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Nitro and amino substitution in the D-ring of 5-(2-dimethylaminoethyl)2,3-methylenedioxy-5H-dibenzo[c,h][1,6] naphthyridin-6-ones : Effect on topoisomerase-I targeting activity and cytotoxicity. / Singh, Sudhir K.; Ruchelman, Alexander L.; Li, Tsai Kun; Liu, Angela; Liu, Leroy-Fong; LaVoie, Edmond J.

In: Journal of Medicinal Chemistry, Vol. 46, No. 11, 22.05.2003, p. 2254-2257.

Research output: Contribution to journalArticle

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AU - LaVoie, Edmond J.

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