Esters and amides of 2,3-dimethoxy-8,9-methylenedioxy-benzo[i] phenanthridine-12-carboxylic acid: Potent cytotoxic and topoisomerase I-targeting agents

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

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44 Citations (Scopus)


The exceptional topoisomerase I-targeting activity and antitumor activity of 5-(2-N,N-dimethylamino)ethyl-8,9-dimethoxy-2,3-methylenedioxy-5H-dibenzo[c,h] [1,6]naphthyridin-6-one (ARC-111, topovale) prompted studies on similarly substituted benzo[i]phenanthridine-12-carboxylic ester and amide derivatives. Among the benzo[i]phenanthridine-12-carboxylic esters evaluated, the 2-(N,N-dimethylamino)ethyl, 2-(N,N-dimethylamino)-1-methylethyl, and 2-(N,N-dimethylamino)-1,1-dimethylethyl esters possessed similar cytotoxicity, ranging from 30 to 55 nM in RPMI8402 and KB3-1 cells. Several of the carboxamide derivatives possess potent topoisomerase I-targeting activity and cytotoxicity. The 2-(N,N-dimethylamino)ethyl, 2-(N,N-diethylamino)ethyl, and 2-(pyrrolidin-1-yl)ethyl amides were among the more cytotoxic benzo[i]phenanthridine-12-carboxylic derivatives, with IC50 values ranging from 0.4 to 5.0 nM in RPMI8402 and KB3-1 cells.

Original languageEnglish
Pages (from-to)6782-6794
Number of pages13
JournalBioorganic and Medicinal Chemistry
Issue number24
Publication statusPublished - Dec 15 2005
Externally publishedYes



  • Antitumor
  • Benzo[i]phenanthridine
  • Cytotoxic
  • Topoisomerase I

ASJC Scopus subject areas

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

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