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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 1a–2c) 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 (hTOPI)...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924348/ https://www.ncbi.nlm.nih.gov/pubmed/33672694 http://dx.doi.org/10.3390/molecules26041133 |
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author | Konkoľová, Eva Hudáčová, Monika Hamuľaková, Slávka Jendželovský, Rastislav Vargová, Jana Ševc, Juraj Fedoročko, Peter Kožurková, Mária |
author_facet | Konkoľová, Eva Hudáčová, Monika Hamuľaková, Slávka Jendželovský, Rastislav Vargová, Jana Ševc, Juraj Fedoročko, Peter Kožurková, Mária |
author_sort | Konkoľová, Eva |
collection | PubMed |
description | A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives 1a–2c) 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 (hTOPI) 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 (1c, 1d = tacrine-(CH(2))(8–9)-coumarin). The most active of the tested compounds, derivatives 1c and 1d, both display longer chains. |
format | Online Article Text |
id | pubmed-7924348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79243482021-03-03 Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines Konkoľová, Eva Hudáčová, Monika Hamuľaková, Slávka Jendželovský, Rastislav Vargová, Jana Ševc, Juraj Fedoročko, Peter Kožurková, Mária Molecules Article A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives 1a–2c) 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 (hTOPI) 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 (1c, 1d = tacrine-(CH(2))(8–9)-coumarin). The most active of the tested compounds, derivatives 1c and 1d, both display longer chains. MDPI 2021-02-20 /pmc/articles/PMC7924348/ /pubmed/33672694 http://dx.doi.org/10.3390/molecules26041133 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Konkoľová, Eva Hudáčová, Monika Hamuľaková, Slávka Jendželovský, Rastislav Vargová, Jana Ševc, Juraj Fedoročko, Peter Kožurková, Mária Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924348/ https://www.ncbi.nlm.nih.gov/pubmed/33672694 http://dx.doi.org/10.3390/molecules26041133 |
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