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

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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
Issue number11
Publication statusPublished - May 22 2003
Externally publishedYes


ASJC Scopus subject areas

  • Organic Chemistry

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