Cytotoxicity and DNA topoisomerase inhibitory activity of benz[f]indole-4,9-dione analogs

Hyen Joo Park, Hyun Jung Lee, Eun Jin Lee, Hye Jin Hwang, Sang Hee Shin, Myung Eun Suh, Choonmi Kim, Hwa Jung Kim, Eun Kyung Seo, Sang Kook Lee

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31 Scopus citations


A series of benz[f]indole-4,9-diones, based on the antitumor activity of 1,4-naphthoquinone, were synthesized and evaluated for their cytotoxic activity in cultured human cancer cell lines A549 (lung cancer), Col2 (colon cancer), and SNU-638 (stomach cancer), and also for the inhibition of human DNA topoisomerases I and II activity in vitro. Several compounds including 2-amino-3-ethoxycarbonyl-N-methyl-benz[f]indole-4,9-dione showed a potential cytotoxic activity judged by IC50 < 20.0 μg/ml in the panel of cancer cell lines. Especially, 2-hydroxy-3-ethoxycarbonyl-N-(3,4-dimethylphenyl) -benz[f]indole-4,9-dione had potential selective cytotoxicity against lung cancer cells (IC50= 0.4 μg/ml)) compared to colon (IC50 > 20.0 μg/ml) and stomach (IC50 > 20.0 μg/ml) cancer cells. To further investigate the cytotoxic mechanism, the effects of test compounds on DNA topoisomerase I and II activities were used. In a topoisomerase I-mediated relaxation assay using human placenta DNA topoisomerase I and supercoiled pHOTI plasmid DNA, 2-amino-3-ethoxycarbonyl-N-(4-fluorophenyl)- benz[f]indole-4,9-dione had the most potent inhibitory activity among the compounds tested. However, most of the compounds showed only weak inhibition of the DNA topoisomerase II-mediated KDNA (Kinetoplast DNA) decatenation assay, except for 2-amino-3-ethoxycarbonyl-N-(4-methylphenyl)-benz[f]indole-4,9-dione and 2-amino-3-ethoxycarbonyl-N-(2-bromoehtyl)-benz[f]indole-4,9-dione with a moderate inhibitory activity. These results suggest that several active compounds had relatively selective inhibitory activity against toposiomearse I compared to toposiomerase II. No obvious correlation was observed between the cytotoxicity of the individual compound and the inhibitory activity of DNA relaxation and decatenation by topoisomerase I and II, respectively, in vitro.

Original languageEnglish
Pages (from-to)1944-1949
Number of pages6
JournalBioscience, Biotechnology and Biochemistry
Issue number9
StatePublished - Sep 2003

Bibliographical note

Funding Information:
This work was supported by a Korea Research Foundation Grant (KRF-2001-005-F00023).


  • Benz[f]indole-4,9-diones
  • Cytotoxicity
  • Topoisomerase I and II


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