Design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action

A series of 116 small-molecule 1-hydroxynaphthalene-2-carboxanilides was designed based on the fragment-based approach and was synthesized according to the microwave-assisted protocol. The biological activity of all of the compounds was tested on human colon carcinoma cell lines including a deleted...

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Autores principales: Spaczyńska, Ewelina, Mrozek-Wilczkiewicz, Anna, Malarz, Katarzyna, Kos, Jiri, Gonec, Tomas, Oravec, Michal, Gawecki, Robert, Bak, Andrzej, Dohanosova, Jana, Kapustikova, Iva, Liptaj, Tibor, Jampilek, Josef, Musiol, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476888/
https://www.ncbi.nlm.nih.gov/pubmed/31011161
http://dx.doi.org/10.1038/s41598-019-42595-y
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author Spaczyńska, Ewelina
Mrozek-Wilczkiewicz, Anna
Malarz, Katarzyna
Kos, Jiri
Gonec, Tomas
Oravec, Michal
Gawecki, Robert
Bak, Andrzej
Dohanosova, Jana
Kapustikova, Iva
Liptaj, Tibor
Jampilek, Josef
Musiol, Robert
author_facet Spaczyńska, Ewelina
Mrozek-Wilczkiewicz, Anna
Malarz, Katarzyna
Kos, Jiri
Gonec, Tomas
Oravec, Michal
Gawecki, Robert
Bak, Andrzej
Dohanosova, Jana
Kapustikova, Iva
Liptaj, Tibor
Jampilek, Josef
Musiol, Robert
author_sort Spaczyńska, Ewelina
collection PubMed
description A series of 116 small-molecule 1-hydroxynaphthalene-2-carboxanilides was designed based on the fragment-based approach and was synthesized according to the microwave-assisted protocol. The biological activity of all of the compounds was tested on human colon carcinoma cell lines including a deleted TP53 tumor suppressor gene. The mechanism of activity was studied according to the p53 status in the cell. Several compounds revealed a good to excellent activity that was similar to or better than the standard anticancer drugs. Some of these appeared to be more active against the p53 null cells than their wild-type counterparts. Intercalating the properties of these compounds could be responsible for their mechanism of action.
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spelling pubmed-64768882019-05-02 Design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action Spaczyńska, Ewelina Mrozek-Wilczkiewicz, Anna Malarz, Katarzyna Kos, Jiri Gonec, Tomas Oravec, Michal Gawecki, Robert Bak, Andrzej Dohanosova, Jana Kapustikova, Iva Liptaj, Tibor Jampilek, Josef Musiol, Robert Sci Rep Article A series of 116 small-molecule 1-hydroxynaphthalene-2-carboxanilides was designed based on the fragment-based approach and was synthesized according to the microwave-assisted protocol. The biological activity of all of the compounds was tested on human colon carcinoma cell lines including a deleted TP53 tumor suppressor gene. The mechanism of activity was studied according to the p53 status in the cell. Several compounds revealed a good to excellent activity that was similar to or better than the standard anticancer drugs. Some of these appeared to be more active against the p53 null cells than their wild-type counterparts. Intercalating the properties of these compounds could be responsible for their mechanism of action. Nature Publishing Group UK 2019-04-23 /pmc/articles/PMC6476888/ /pubmed/31011161 http://dx.doi.org/10.1038/s41598-019-42595-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Spaczyńska, Ewelina
Mrozek-Wilczkiewicz, Anna
Malarz, Katarzyna
Kos, Jiri
Gonec, Tomas
Oravec, Michal
Gawecki, Robert
Bak, Andrzej
Dohanosova, Jana
Kapustikova, Iva
Liptaj, Tibor
Jampilek, Josef
Musiol, Robert
Design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action
title Design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action
title_full Design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action
title_fullStr Design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action
title_full_unstemmed Design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action
title_short Design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action
title_sort design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476888/
https://www.ncbi.nlm.nih.gov/pubmed/31011161
http://dx.doi.org/10.1038/s41598-019-42595-y
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