Cargando…

Design and Synthesis of New 1,3,5‐Trisubstituted Triazines for the Treatment of Cancer and Inflammation

Low‐molecular‐weight synthetic molecules 1 with the general 2‐(fluorophenylamino)‐4,6‐disubstituted 1,3,5‐triazine structure and showing anti‐inflammatory and anticancer activities were explored. Structure–activity relationship studies demonstrated the importance of the aminopentyl chain, the 3‐ or...

Descripción completa

Detalles Bibliográficos
Autores principales: Zacharie, Boulos, Abbott, Shaun D., Duceppe, Jean‐Simon, Gagnon, Lyne, Grouix, Brigitte, Geerts, Lilianne, Gervais, Liette, Sarra‐Bournet, François, Perron, Valérie, Wilb, Nicole, Penney, Christopher L., Laurin, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148406/
https://www.ncbi.nlm.nih.gov/pubmed/30258746
http://dx.doi.org/10.1002/open.201800136
_version_ 1783356739209396224
author Zacharie, Boulos
Abbott, Shaun D.
Duceppe, Jean‐Simon
Gagnon, Lyne
Grouix, Brigitte
Geerts, Lilianne
Gervais, Liette
Sarra‐Bournet, François
Perron, Valérie
Wilb, Nicole
Penney, Christopher L.
Laurin, Pierre
author_facet Zacharie, Boulos
Abbott, Shaun D.
Duceppe, Jean‐Simon
Gagnon, Lyne
Grouix, Brigitte
Geerts, Lilianne
Gervais, Liette
Sarra‐Bournet, François
Perron, Valérie
Wilb, Nicole
Penney, Christopher L.
Laurin, Pierre
author_sort Zacharie, Boulos
collection PubMed
description Low‐molecular‐weight synthetic molecules 1 with the general 2‐(fluorophenylamino)‐4,6‐disubstituted 1,3,5‐triazine structure and showing anti‐inflammatory and anticancer activities were explored. Structure–activity relationship studies demonstrated the importance of the aminopentyl chain, the 3‐ or 4‐fluorophenylaniline component, and the presence of at least one substituent, such as a tyramine moiety, attached directly to the triazine ring as essential for good activity. These compounds, represented by leads 4‐{2‐[4‐(5‐Aminopentylamino)‐6‐(3‐fluorophenylamino)‐1,3,5‐triazin‐2‐ylamino]ethyl}phenol (6) and 4‐{2‐[4‐(5‐Aminopentylamino)‐6‐(4‐fluorophenylamino)‐1,3,5‐triazin‐2‐ylamino]ethyl}phenol (10), displayed moderate and significant in vitro and in vivo dual activities, respectively, and address the molecular link between inflammation and cancer. Compound 10 demonstrated significant antitumor efficacy upon administration by the oral and intravenous routes in several animal models. This class of triazine compounds is new, safe, and nontoxic and offers a novel approach to the treatment of inflammation and cancer.
format Online
Article
Text
id pubmed-6148406
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-61484062018-09-26 Design and Synthesis of New 1,3,5‐Trisubstituted Triazines for the Treatment of Cancer and Inflammation Zacharie, Boulos Abbott, Shaun D. Duceppe, Jean‐Simon Gagnon, Lyne Grouix, Brigitte Geerts, Lilianne Gervais, Liette Sarra‐Bournet, François Perron, Valérie Wilb, Nicole Penney, Christopher L. Laurin, Pierre ChemistryOpen Full Papers Low‐molecular‐weight synthetic molecules 1 with the general 2‐(fluorophenylamino)‐4,6‐disubstituted 1,3,5‐triazine structure and showing anti‐inflammatory and anticancer activities were explored. Structure–activity relationship studies demonstrated the importance of the aminopentyl chain, the 3‐ or 4‐fluorophenylaniline component, and the presence of at least one substituent, such as a tyramine moiety, attached directly to the triazine ring as essential for good activity. These compounds, represented by leads 4‐{2‐[4‐(5‐Aminopentylamino)‐6‐(3‐fluorophenylamino)‐1,3,5‐triazin‐2‐ylamino]ethyl}phenol (6) and 4‐{2‐[4‐(5‐Aminopentylamino)‐6‐(4‐fluorophenylamino)‐1,3,5‐triazin‐2‐ylamino]ethyl}phenol (10), displayed moderate and significant in vitro and in vivo dual activities, respectively, and address the molecular link between inflammation and cancer. Compound 10 demonstrated significant antitumor efficacy upon administration by the oral and intravenous routes in several animal models. This class of triazine compounds is new, safe, and nontoxic and offers a novel approach to the treatment of inflammation and cancer. John Wiley and Sons Inc. 2018-09-21 /pmc/articles/PMC6148406/ /pubmed/30258746 http://dx.doi.org/10.1002/open.201800136 Text en © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Full Papers
Zacharie, Boulos
Abbott, Shaun D.
Duceppe, Jean‐Simon
Gagnon, Lyne
Grouix, Brigitte
Geerts, Lilianne
Gervais, Liette
Sarra‐Bournet, François
Perron, Valérie
Wilb, Nicole
Penney, Christopher L.
Laurin, Pierre
Design and Synthesis of New 1,3,5‐Trisubstituted Triazines for the Treatment of Cancer and Inflammation
title Design and Synthesis of New 1,3,5‐Trisubstituted Triazines for the Treatment of Cancer and Inflammation
title_full Design and Synthesis of New 1,3,5‐Trisubstituted Triazines for the Treatment of Cancer and Inflammation
title_fullStr Design and Synthesis of New 1,3,5‐Trisubstituted Triazines for the Treatment of Cancer and Inflammation
title_full_unstemmed Design and Synthesis of New 1,3,5‐Trisubstituted Triazines for the Treatment of Cancer and Inflammation
title_short Design and Synthesis of New 1,3,5‐Trisubstituted Triazines for the Treatment of Cancer and Inflammation
title_sort design and synthesis of new 1,3,5‐trisubstituted triazines for the treatment of cancer and inflammation
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148406/
https://www.ncbi.nlm.nih.gov/pubmed/30258746
http://dx.doi.org/10.1002/open.201800136
work_keys_str_mv AT zacharieboulos designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT abbottshaund designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT duceppejeansimon designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT gagnonlyne designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT grouixbrigitte designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT geertslilianne designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT gervaisliette designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT sarrabournetfrancois designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT perronvalerie designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT wilbnicole designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT penneychristopherl designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation
AT laurinpierre designandsynthesisofnew135trisubstitutedtriazinesforthetreatmentofcancerandinflammation