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In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers

A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12–17 and urea heterodimers 18–22, and to measure interference with type I and II topoisomerases. Their biological profile was also inspec...

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Autores principales: Janockova, Jana, Korabecny, Jan, Plsikova, Jana, Babkova, Katerina, Konkolova, Eva, Kucerova, Dana, Vargova, Jana, Koval, Jan, Jendzelovsky, Rastislav, Fedorocko, Peter, Kasparkova, Jana, Brabec, Viktor, Rosocha, Jan, Soukup, Ondrej, Hamulakova, Slavka, Kuca, Kamil, Kozurkova, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450562/
https://www.ncbi.nlm.nih.gov/pubmed/30938202
http://dx.doi.org/10.1080/14756366.2019.1593159
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author Janockova, Jana
Korabecny, Jan
Plsikova, Jana
Babkova, Katerina
Konkolova, Eva
Kucerova, Dana
Vargova, Jana
Koval, Jan
Jendzelovsky, Rastislav
Fedorocko, Peter
Kasparkova, Jana
Brabec, Viktor
Rosocha, Jan
Soukup, Ondrej
Hamulakova, Slavka
Kuca, Kamil
Kozurkova, Maria
author_facet Janockova, Jana
Korabecny, Jan
Plsikova, Jana
Babkova, Katerina
Konkolova, Eva
Kucerova, Dana
Vargova, Jana
Koval, Jan
Jendzelovsky, Rastislav
Fedorocko, Peter
Kasparkova, Jana
Brabec, Viktor
Rosocha, Jan
Soukup, Ondrej
Hamulakova, Slavka
Kuca, Kamil
Kozurkova, Maria
author_sort Janockova, Jana
collection PubMed
description A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12–17 and urea heterodimers 18–22, and to measure interference with type I and II topoisomerases. Their biological profile was also inspected in vitro on the HL-60 cell line using different flow cytometric techniques (cell cycle distribution, detection of mitochondrial membrane potential dissipation, and analysis of metabolic activity/viability). The compounds exhibited a profound inhibitory effect on topoisomerase activity (e.g. compound 22 inhibited type I topoisomerase at 1 µM concentration). The treatment of HL-60 cells with the studied compounds showed inhibition of cell growth especially with hybrids containing thiourea (14–17) and urea moieties (21 and 22). Moreover, treatment of human dermal fibroblasts with the studied compounds did not indicate significant cytotoxicity. The observed results suggest beneficial selectivity of the heterodimers as potential drugs to target cancer cells.
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spelling pubmed-64505622019-04-15 In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers Janockova, Jana Korabecny, Jan Plsikova, Jana Babkova, Katerina Konkolova, Eva Kucerova, Dana Vargova, Jana Koval, Jan Jendzelovsky, Rastislav Fedorocko, Peter Kasparkova, Jana Brabec, Viktor Rosocha, Jan Soukup, Ondrej Hamulakova, Slavka Kuca, Kamil Kozurkova, Maria J Enzyme Inhib Med Chem Research Article A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12–17 and urea heterodimers 18–22, and to measure interference with type I and II topoisomerases. Their biological profile was also inspected in vitro on the HL-60 cell line using different flow cytometric techniques (cell cycle distribution, detection of mitochondrial membrane potential dissipation, and analysis of metabolic activity/viability). The compounds exhibited a profound inhibitory effect on topoisomerase activity (e.g. compound 22 inhibited type I topoisomerase at 1 µM concentration). The treatment of HL-60 cells with the studied compounds showed inhibition of cell growth especially with hybrids containing thiourea (14–17) and urea moieties (21 and 22). Moreover, treatment of human dermal fibroblasts with the studied compounds did not indicate significant cytotoxicity. The observed results suggest beneficial selectivity of the heterodimers as potential drugs to target cancer cells. Taylor & Francis 2019-04-02 /pmc/articles/PMC6450562/ /pubmed/30938202 http://dx.doi.org/10.1080/14756366.2019.1593159 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Janockova, Jana
Korabecny, Jan
Plsikova, Jana
Babkova, Katerina
Konkolova, Eva
Kucerova, Dana
Vargova, Jana
Koval, Jan
Jendzelovsky, Rastislav
Fedorocko, Peter
Kasparkova, Jana
Brabec, Viktor
Rosocha, Jan
Soukup, Ondrej
Hamulakova, Slavka
Kuca, Kamil
Kozurkova, Maria
In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers
title In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers
title_full In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers
title_fullStr In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers
title_full_unstemmed In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers
title_short In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers
title_sort in vitro investigating of anticancer activity of new 7-meota-tacrine heterodimers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450562/
https://www.ncbi.nlm.nih.gov/pubmed/30938202
http://dx.doi.org/10.1080/14756366.2019.1593159
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