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

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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
Volume13
Issue number24
DOIs
Publication statusPublished - Dec 15 2005
Externally publishedYes

Fingerprint

Phenanthridines
Type I DNA Topoisomerase
Amides
Esters
Cytotoxicity
Derivatives
Inhibitory Concentration 50
2,3-dimethoxy-8,9-methylenedioxy-benzo(i)phenanthridine-12-carboxylic acid
topovale

Keywords

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

ASJC Scopus subject areas

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

Cite this

Esters and amides of 2,3-dimethoxy-8,9-methylenedioxy-benzo[i] phenanthridine-12-carboxylic acid : Potent cytotoxic and topoisomerase I-targeting agents. / Zhu, Shejin; Ruchelman, Alexander L.; Zhou, Nai; Liu, Angela A.; Liu, Leroy-Fong; LaVoie, Edmond J.

In: Bioorganic and Medicinal Chemistry, Vol. 13, No. 24, 15.12.2005, p. 6782-6794.

Research output: Contribution to journalArticle

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AU - Zhou, Nai

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