Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines
A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives <b>1a</b>–<b>2c</b>) in order to test the compounds’ ability to inhibit both cancer cell growth and topoisomerase I and II activity. The abi...
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MDPI AG
2021-02-01
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| Online Access: | https://www.mdpi.com/1420-3049/26/4/1133 |
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| author | Eva Konkoľová Monika Hudáčová Slávka Hamuľaková Rastislav Jendželovský Jana Vargová Juraj Ševc Peter Fedoročko Mária Kožurková |
| author_facet | Eva Konkoľová Monika Hudáčová Slávka Hamuľaková Rastislav Jendželovský Jana Vargová Juraj Ševc Peter Fedoročko Mária Kožurková |
| author_sort | Eva Konkoľová |
| collection | DOAJ |
| description | A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives <b>1a</b>–<b>2c</b>) in order to test the compounds’ ability to inhibit both cancer cell growth and topoisomerase I and II activity. The ability of human topoisomerase I (<i>h</i>TOPI) and II to relax supercoiled plasmid DNA in the presence of various concentrations of the tacrine-coumarin hybrid molecules was studied with agarose gel electrophoresis. The biological activities of the derivatives were studied using MTT assays, clonogenic assays, cell cycle analysis and quantification of cell number and viability. The content and localization of the derivatives in the cells were analysed using flow cytometry and confocal microscopy. All of the studied compounds were found to have inhibited topoisomerase I activity completely. The effect of the tacrine-coumarin hybrid compounds on cancer cells is likely to be dependent on the length of the chain between the tacrine and coumarin moieties (<b>1c</b>, <b>1d</b> = tacrine-(CH<sub>2</sub>)<sub>8–9</sub>-coumarin). The most active of the tested compounds, derivatives <b>1c</b> and <b>1d</b>, both display longer chains. |
| first_indexed | 2024-03-09T00:40:11Z |
| format | Article |
| id | doaj.art-0af2efc10a534d30b4ed3b66d04503a4 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T00:40:11Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0af2efc10a534d30b4ed3b66d04503a42023-12-11T17:49:16ZengMDPI AGMolecules1420-30492021-02-01264113310.3390/molecules26041133Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell LinesEva Konkoľová0Monika Hudáčová1Slávka Hamuľaková2Rastislav Jendželovský3Jana Vargová4Juraj Ševc5Peter Fedoročko6Mária Kožurková7Department of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Kosice, 041 80 Košice, SlovakiaDepartment of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Kosice, 041 80 Košice, SlovakiaDepartment of Organic Chemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Košice, 041 80 Košice, SlovakiaDepartment of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, 041 80 Košice, SlovakiaDepartment of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, 041 80 Košice, SlovakiaDepartment of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, 041 80 Košice, SlovakiaDepartment of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, 041 80 Košice, SlovakiaDepartment of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Kosice, 041 80 Košice, SlovakiaA549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives <b>1a</b>–<b>2c</b>) in order to test the compounds’ ability to inhibit both cancer cell growth and topoisomerase I and II activity. The ability of human topoisomerase I (<i>h</i>TOPI) and II to relax supercoiled plasmid DNA in the presence of various concentrations of the tacrine-coumarin hybrid molecules was studied with agarose gel electrophoresis. The biological activities of the derivatives were studied using MTT assays, clonogenic assays, cell cycle analysis and quantification of cell number and viability. The content and localization of the derivatives in the cells were analysed using flow cytometry and confocal microscopy. All of the studied compounds were found to have inhibited topoisomerase I activity completely. The effect of the tacrine-coumarin hybrid compounds on cancer cells is likely to be dependent on the length of the chain between the tacrine and coumarin moieties (<b>1c</b>, <b>1d</b> = tacrine-(CH<sub>2</sub>)<sub>8–9</sub>-coumarin). The most active of the tested compounds, derivatives <b>1c</b> and <b>1d</b>, both display longer chains.https://www.mdpi.com/1420-3049/26/4/1133tacrine-coumarin derivativesDNAtopoisomerases I, IIcytotoxicitylung carcinoma cellsA549 |
| spellingShingle | Eva Konkoľová Monika Hudáčová Slávka Hamuľaková Rastislav Jendželovský Jana Vargová Juraj Ševc Peter Fedoročko Mária Kožurková Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines Molecules tacrine-coumarin derivatives DNA topoisomerases I, II cytotoxicity lung carcinoma cells A549 |
| title | Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines |
| title_full | Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines |
| title_fullStr | Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines |
| title_full_unstemmed | Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines |
| title_short | Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines |
| title_sort | tacrine coumarin derivatives as topoisomerase inhibitors with antitumor effects on a549 human lung carcinoma cancer cell lines |
| topic | tacrine-coumarin derivatives DNA topoisomerases I, II cytotoxicity lung carcinoma cells A549 |
| url | https://www.mdpi.com/1420-3049/26/4/1133 |
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