Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells

In the search for new antitumor agents, aminophosphonic acids and their derivatives based on octahydroquinoxalin-2(1H)-one scaffold were obtained and their cytotoxic properties and a mechanism of action were evaluated. Phosphonic acid and phosphonate moieties increased the antiproliferative activity...

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Autores principales: Iwanejko, Jakub, Wojaczyńska, Elżbieta, Turlej, Eliza, Maciejewska, Magdalena, Wietrzyk, Joanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287629/
https://www.ncbi.nlm.nih.gov/pubmed/32455965
http://dx.doi.org/10.3390/ma13102393
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author Iwanejko, Jakub
Wojaczyńska, Elżbieta
Turlej, Eliza
Maciejewska, Magdalena
Wietrzyk, Joanna
author_facet Iwanejko, Jakub
Wojaczyńska, Elżbieta
Turlej, Eliza
Maciejewska, Magdalena
Wietrzyk, Joanna
author_sort Iwanejko, Jakub
collection PubMed
description In the search for new antitumor agents, aminophosphonic acids and their derivatives based on octahydroquinoxalin-2(1H)-one scaffold were obtained and their cytotoxic properties and a mechanism of action were evaluated. Phosphonic acid and phosphonate moieties increased the antiproliferative activity in comparison to phenolic Mannich bases previously reported. Most of the obtained compounds revealed a strong antiproliferative effect against leukemia cell line (MV-4-11) with simultaneous low cytotoxicity against normal cell line (mouse fibroblasts-BALB/3T3). The most active compound was diphenyl-[(1R,6R)-3-oxo-2,5-diazabicyclo[4.4.0]dec-4-yl]phosphonate. Preliminary evaluation of the mechanism of action showed the proapoptotic effect associated with caspase 3/7 induction.
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spelling pubmed-72876292020-06-15 Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells Iwanejko, Jakub Wojaczyńska, Elżbieta Turlej, Eliza Maciejewska, Magdalena Wietrzyk, Joanna Materials (Basel) Article In the search for new antitumor agents, aminophosphonic acids and their derivatives based on octahydroquinoxalin-2(1H)-one scaffold were obtained and their cytotoxic properties and a mechanism of action were evaluated. Phosphonic acid and phosphonate moieties increased the antiproliferative activity in comparison to phenolic Mannich bases previously reported. Most of the obtained compounds revealed a strong antiproliferative effect against leukemia cell line (MV-4-11) with simultaneous low cytotoxicity against normal cell line (mouse fibroblasts-BALB/3T3). The most active compound was diphenyl-[(1R,6R)-3-oxo-2,5-diazabicyclo[4.4.0]dec-4-yl]phosphonate. Preliminary evaluation of the mechanism of action showed the proapoptotic effect associated with caspase 3/7 induction. MDPI 2020-05-22 /pmc/articles/PMC7287629/ /pubmed/32455965 http://dx.doi.org/10.3390/ma13102393 Text en © 2020 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
Iwanejko, Jakub
Wojaczyńska, Elżbieta
Turlej, Eliza
Maciejewska, Magdalena
Wietrzyk, Joanna
Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells
title Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells
title_full Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells
title_fullStr Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells
title_full_unstemmed Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells
title_short Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells
title_sort octahydroquinoxalin-2(1h)-one-based aminophosphonic acids and their derivatives—biological activity towards cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287629/
https://www.ncbi.nlm.nih.gov/pubmed/32455965
http://dx.doi.org/10.3390/ma13102393
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