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Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II
Olivacine and ellipticine are model anticancer drugs acting as topoisomerase II inhibitors. Here, we present investigations performed on four olivacine derivatives in light of their antitumor activity. The aim of this study was to identify the best antitumor compound among the four tested olivacine...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395211/ https://www.ncbi.nlm.nih.gov/pubmed/34445198 http://dx.doi.org/10.3390/ijms22168492 |
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author | Tylińska, Beata Dobosz, Agnieszka Spychała, Jan Cwynar-Zając, Łucja Czyżnikowska, Żaneta Kuźniarski, Amadeusz Gębarowski, Tomasz |
author_facet | Tylińska, Beata Dobosz, Agnieszka Spychała, Jan Cwynar-Zając, Łucja Czyżnikowska, Żaneta Kuźniarski, Amadeusz Gębarowski, Tomasz |
author_sort | Tylińska, Beata |
collection | PubMed |
description | Olivacine and ellipticine are model anticancer drugs acting as topoisomerase II inhibitors. Here, we present investigations performed on four olivacine derivatives in light of their antitumor activity. The aim of this study was to identify the best antitumor compound among the four tested olivacine derivatives. The study was performed using CCRF/CEM and MCF-7 cell lines. Comet assay, polarography, inhibition of topoisomerase II activity, histone acetylation, and molecular docking studies were performed. Each tested compound displayed interaction with DNA and topoisomerase II, but did not cause histone acetylation. Compound 2 (9-methoxy-5,6-dimethyl-1-({[1-hydroxy-2-(hydroxymethyl)butan-2-yl]amino}methyl)-6H-pyrido[4,3-b]carbazole) was found to be the best candidate as an anticancer drug because it had the highest affinity for topoisomerase II and caused the least genotoxic damage in cells. |
format | Online Article Text |
id | pubmed-8395211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83952112021-08-28 Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II Tylińska, Beata Dobosz, Agnieszka Spychała, Jan Cwynar-Zając, Łucja Czyżnikowska, Żaneta Kuźniarski, Amadeusz Gębarowski, Tomasz Int J Mol Sci Article Olivacine and ellipticine are model anticancer drugs acting as topoisomerase II inhibitors. Here, we present investigations performed on four olivacine derivatives in light of their antitumor activity. The aim of this study was to identify the best antitumor compound among the four tested olivacine derivatives. The study was performed using CCRF/CEM and MCF-7 cell lines. Comet assay, polarography, inhibition of topoisomerase II activity, histone acetylation, and molecular docking studies were performed. Each tested compound displayed interaction with DNA and topoisomerase II, but did not cause histone acetylation. Compound 2 (9-methoxy-5,6-dimethyl-1-({[1-hydroxy-2-(hydroxymethyl)butan-2-yl]amino}methyl)-6H-pyrido[4,3-b]carbazole) was found to be the best candidate as an anticancer drug because it had the highest affinity for topoisomerase II and caused the least genotoxic damage in cells. MDPI 2021-08-06 /pmc/articles/PMC8395211/ /pubmed/34445198 http://dx.doi.org/10.3390/ijms22168492 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tylińska, Beata Dobosz, Agnieszka Spychała, Jan Cwynar-Zając, Łucja Czyżnikowska, Żaneta Kuźniarski, Amadeusz Gębarowski, Tomasz Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II |
title | Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II |
title_full | Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II |
title_fullStr | Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II |
title_full_unstemmed | Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II |
title_short | Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II |
title_sort | evaluation of interactions of selected olivacine derivatives with dna and topoisomerase ii |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395211/ https://www.ncbi.nlm.nih.gov/pubmed/34445198 http://dx.doi.org/10.3390/ijms22168492 |
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