Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors

Two novel series of diaryl urea derivatives 5a–i and 13a–l were synthesized and evaluated for their cytotoxicity against H-460, HT-29, A549, and MDA-MB-231 cancer cell lines in vitro. Therein, 4-aminoquinazolinyl-diaryl urea derivatives 5a–i demonstrated significant activity, and seven of them are m...

Descripción completa

Detalles Bibliográficos
Autores principales: Jiang, Nan, Bu, Yanxin, Wang, Yu, Nie, Minhua, Zhang, Dajun, Zhai, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273962/
https://www.ncbi.nlm.nih.gov/pubmed/27869742
http://dx.doi.org/10.3390/molecules21111572
_version_ 1783377508201136128
author Jiang, Nan
Bu, Yanxin
Wang, Yu
Nie, Minhua
Zhang, Dajun
Zhai, Xin
author_facet Jiang, Nan
Bu, Yanxin
Wang, Yu
Nie, Minhua
Zhang, Dajun
Zhai, Xin
author_sort Jiang, Nan
collection PubMed
description Two novel series of diaryl urea derivatives 5a–i and 13a–l were synthesized and evaluated for their cytotoxicity against H-460, HT-29, A549, and MDA-MB-231 cancer cell lines in vitro. Therein, 4-aminoquinazolinyl-diaryl urea derivatives 5a–i demonstrated significant activity, and seven of them are more active than sorafenib, with IC(50) values ranging from 0.089 to 5.46 μM. Especially, compound 5a exhibited the most active potency both in cellular (IC(50) = 0.15, 0.089, 0.36, and 0.75 μM, respectively) and enzymatic assay (IC(50) = 56 nM against EGFR), representing a promising lead for further optimization.
format Online
Article
Text
id pubmed-6273962
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62739622018-12-28 Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors Jiang, Nan Bu, Yanxin Wang, Yu Nie, Minhua Zhang, Dajun Zhai, Xin Molecules Article Two novel series of diaryl urea derivatives 5a–i and 13a–l were synthesized and evaluated for their cytotoxicity against H-460, HT-29, A549, and MDA-MB-231 cancer cell lines in vitro. Therein, 4-aminoquinazolinyl-diaryl urea derivatives 5a–i demonstrated significant activity, and seven of them are more active than sorafenib, with IC(50) values ranging from 0.089 to 5.46 μM. Especially, compound 5a exhibited the most active potency both in cellular (IC(50) = 0.15, 0.089, 0.36, and 0.75 μM, respectively) and enzymatic assay (IC(50) = 56 nM against EGFR), representing a promising lead for further optimization. MDPI 2016-11-18 /pmc/articles/PMC6273962/ /pubmed/27869742 http://dx.doi.org/10.3390/molecules21111572 Text en © 2016 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
Jiang, Nan
Bu, Yanxin
Wang, Yu
Nie, Minhua
Zhang, Dajun
Zhai, Xin
Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors
title Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors
title_full Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors
title_fullStr Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors
title_full_unstemmed Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors
title_short Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors
title_sort design, synthesis and structure-activity relationships of novel diaryl urea derivatives as potential egfr inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273962/
https://www.ncbi.nlm.nih.gov/pubmed/27869742
http://dx.doi.org/10.3390/molecules21111572
work_keys_str_mv AT jiangnan designsynthesisandstructureactivityrelationshipsofnoveldiarylureaderivativesaspotentialegfrinhibitors
AT buyanxin designsynthesisandstructureactivityrelationshipsofnoveldiarylureaderivativesaspotentialegfrinhibitors
AT wangyu designsynthesisandstructureactivityrelationshipsofnoveldiarylureaderivativesaspotentialegfrinhibitors
AT nieminhua designsynthesisandstructureactivityrelationshipsofnoveldiarylureaderivativesaspotentialegfrinhibitors
AT zhangdajun designsynthesisandstructureactivityrelationshipsofnoveldiarylureaderivativesaspotentialegfrinhibitors
AT zhaixin designsynthesisandstructureactivityrelationshipsofnoveldiarylureaderivativesaspotentialegfrinhibitors

Ejemplares similares