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Cytotoxicity and DNA topoisomerase inhibitory activity of benz[f]indole-4,9-dione analogs
- Cytotoxicity and DNA topoisomerase inhibitory activity of benz[f]indole-4,9-dione analogs
- Park H.J.; Lee H.-J.; Lee E.-J.; Hwang H.J.; Shin S.-H.; Suh M.-E.; Kim C.; Kim H.J.; Seo E.-K.; Lee S.K.
- Ewha Authors
- 김춘미; 김화정; 이상국; 서은경
- SCOPUS Author ID
- 김춘미; 김화정; 서은경
- Issue Date
- Journal Title
- Bioscience, Biotechnology and Biochemistry
- vol. 67, no. 9, pp. 1944 - 1949
- SCI; SCIE; SCOPUS
- 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 IC 50 < 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 (IC 50= 0.4 μg/ml)) compared to colon (IC 50 > 20.0 μg/ml) and stomach (IC 50 > 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.
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