Open AccessDesign and Synthesis of New 1,3,5‐Trisubstituted Triazines for the Treatment of Cancer and Inflammation
Author(s) -
Zacharie Boulos,
Abbott Shaun D.,
Duceppe JeanSimon,
Gag Lyne,
Grouix Brigitte,
Geerts Lilianne,
Gervais Liette,
SarraBournet François,
Perron Valérie,
Wilb Nicole,
Penney Christopher L.,
Laurin Pierre
Publication year - 2018
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.201800136
Subject(s) - substituent , chemistry , moiety , in vivo , triazine , in vitro , stereochemistry , combinatorial chemistry , cancer , inflammation , molecule , structure–activity relationship , pharmacology , biochemistry , organic chemistry , medicine , biology , immunology , microbiology and biotechnology
Abstract 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.