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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...

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Autores principales: Tylińska, Beata, Dobosz, Agnieszka, Spychała, Jan, Cwynar-Zając, Łucja, Czyżnikowska, Żaneta, Kuźniarski, Amadeusz, Gębarowski, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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