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Anti-Cancer Activity of Phenyl and Pyrid-2-yl 1,3-Substituted Benzo[1,2,4]triazin-7-ones and Stable Free Radical Precursors

Cell viability studies for benzo[1,2,4]triazin-7-ones and 1,2,4-benzotriazinyl (Blatter-type) radical precursors are described with comparisons made with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). All of the stable free radicals were several orders of magnitude less cytotoxic than the benzo[1,2,4...

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Autores principales: Keane, Lee-Ann J., Mirallai, Styliana I., Sweeney, Martin, Carty, Michael P., Zissimou, Georgia A., Berezin, Andrey A., Koutentis, Panayiotis A., Aldabbagh, Fawaz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017941/
https://www.ncbi.nlm.nih.gov/pubmed/29510488
http://dx.doi.org/10.3390/molecules23030574
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author Keane, Lee-Ann J.
Mirallai, Styliana I.
Sweeney, Martin
Carty, Michael P.
Zissimou, Georgia A.
Berezin, Andrey A.
Koutentis, Panayiotis A.
Aldabbagh, Fawaz
author_facet Keane, Lee-Ann J.
Mirallai, Styliana I.
Sweeney, Martin
Carty, Michael P.
Zissimou, Georgia A.
Berezin, Andrey A.
Koutentis, Panayiotis A.
Aldabbagh, Fawaz
author_sort Keane, Lee-Ann J.
collection PubMed
description Cell viability studies for benzo[1,2,4]triazin-7-ones and 1,2,4-benzotriazinyl (Blatter-type) radical precursors are described with comparisons made with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). All of the stable free radicals were several orders of magnitude less cytotoxic than the benzo[1,2,4]triazin-7-ones. The synthesis and evaluation of two new pyrid-2-yl benzo[1,2,4]triazin-7-ones are described, where altering the 1,3-substitution from phenyl to pyrid-2-yl increased cytotoxicity against most cancer cell lines, as indicated using National Cancer Institute (NCI) one-dose testing. COMPARE analysis of five-dose testing data from the NCI showed very strong correlations to the naturally occurring anti-cancer compound pleurotin. COMPARE is program, which analyzes similarities in cytotoxicity data of compounds, and enables quantitative expression as Pearson correlation coefficients. Compounds were also evaluated using the independent MTT assay, which was compared with SRB assay data generated at the NCI.
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spelling pubmed-60179412018-11-13 Anti-Cancer Activity of Phenyl and Pyrid-2-yl 1,3-Substituted Benzo[1,2,4]triazin-7-ones and Stable Free Radical Precursors Keane, Lee-Ann J. Mirallai, Styliana I. Sweeney, Martin Carty, Michael P. Zissimou, Georgia A. Berezin, Andrey A. Koutentis, Panayiotis A. Aldabbagh, Fawaz Molecules Article Cell viability studies for benzo[1,2,4]triazin-7-ones and 1,2,4-benzotriazinyl (Blatter-type) radical precursors are described with comparisons made with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). All of the stable free radicals were several orders of magnitude less cytotoxic than the benzo[1,2,4]triazin-7-ones. The synthesis and evaluation of two new pyrid-2-yl benzo[1,2,4]triazin-7-ones are described, where altering the 1,3-substitution from phenyl to pyrid-2-yl increased cytotoxicity against most cancer cell lines, as indicated using National Cancer Institute (NCI) one-dose testing. COMPARE analysis of five-dose testing data from the NCI showed very strong correlations to the naturally occurring anti-cancer compound pleurotin. COMPARE is program, which analyzes similarities in cytotoxicity data of compounds, and enables quantitative expression as Pearson correlation coefficients. Compounds were also evaluated using the independent MTT assay, which was compared with SRB assay data generated at the NCI. MDPI 2018-03-03 /pmc/articles/PMC6017941/ /pubmed/29510488 http://dx.doi.org/10.3390/molecules23030574 Text en © 2018 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
Keane, Lee-Ann J.
Mirallai, Styliana I.
Sweeney, Martin
Carty, Michael P.
Zissimou, Georgia A.
Berezin, Andrey A.
Koutentis, Panayiotis A.
Aldabbagh, Fawaz
Anti-Cancer Activity of Phenyl and Pyrid-2-yl 1,3-Substituted Benzo[1,2,4]triazin-7-ones and Stable Free Radical Precursors
title Anti-Cancer Activity of Phenyl and Pyrid-2-yl 1,3-Substituted Benzo[1,2,4]triazin-7-ones and Stable Free Radical Precursors
title_full Anti-Cancer Activity of Phenyl and Pyrid-2-yl 1,3-Substituted Benzo[1,2,4]triazin-7-ones and Stable Free Radical Precursors
title_fullStr Anti-Cancer Activity of Phenyl and Pyrid-2-yl 1,3-Substituted Benzo[1,2,4]triazin-7-ones and Stable Free Radical Precursors
title_full_unstemmed Anti-Cancer Activity of Phenyl and Pyrid-2-yl 1,3-Substituted Benzo[1,2,4]triazin-7-ones and Stable Free Radical Precursors
title_short Anti-Cancer Activity of Phenyl and Pyrid-2-yl 1,3-Substituted Benzo[1,2,4]triazin-7-ones and Stable Free Radical Precursors
title_sort anti-cancer activity of phenyl and pyrid-2-yl 1,3-substituted benzo[1,2,4]triazin-7-ones and stable free radical precursors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017941/
https://www.ncbi.nlm.nih.gov/pubmed/29510488
http://dx.doi.org/10.3390/molecules23030574
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