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Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit
Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by (1)H-NMR, (1)(3)C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3 cancer ce...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332012/ https://www.ncbi.nlm.nih.gov/pubmed/26512636 http://dx.doi.org/10.3390/molecules201019361 |
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author | Wu, Chunjiang Wang, Min Tang, Qidong Luo, Rong Chen, Le Zheng, Pengwu Zhu, Wufu |
author_facet | Wu, Chunjiang Wang, Min Tang, Qidong Luo, Rong Chen, Le Zheng, Pengwu Zhu, Wufu |
author_sort | Wu, Chunjiang |
collection | PubMed |
description | Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by (1)H-NMR, (1)(3)C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3 cancer cell lines. Some of the compounds showed moderate cytotoxic activity, especially compounds 1-(2,4-difluorophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6c) and 1-(4-bromophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6f) with the IC(50) values against four cancer cell lines ranging from 16.54 ± 1.22 to 63.92 ± 1.81 μM, respectively. Inhibitory rates against vascular endothelial growth factor receptor-2 (VEGFR2/KDR) kinase at 10 μM of target compounds were further carried out in this paper in order to investigate the target of these compounds. Structure-activity relationships (SARs) and docking studies indicated that the sulfonylurea unit was important to these kinds of compounds. None of the substitutions in the phenoxy group and small halogen atoms such as 2,4-difluoro substitution of the aryl group contributed to the activity. The results suggested that sulfonylurea sorafenib analogs are worthy of further study. |
format | Online Article Text |
id | pubmed-6332012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63320122019-01-24 Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit Wu, Chunjiang Wang, Min Tang, Qidong Luo, Rong Chen, Le Zheng, Pengwu Zhu, Wufu Molecules Article Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by (1)H-NMR, (1)(3)C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3 cancer cell lines. Some of the compounds showed moderate cytotoxic activity, especially compounds 1-(2,4-difluorophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6c) and 1-(4-bromophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6f) with the IC(50) values against four cancer cell lines ranging from 16.54 ± 1.22 to 63.92 ± 1.81 μM, respectively. Inhibitory rates against vascular endothelial growth factor receptor-2 (VEGFR2/KDR) kinase at 10 μM of target compounds were further carried out in this paper in order to investigate the target of these compounds. Structure-activity relationships (SARs) and docking studies indicated that the sulfonylurea unit was important to these kinds of compounds. None of the substitutions in the phenoxy group and small halogen atoms such as 2,4-difluoro substitution of the aryl group contributed to the activity. The results suggested that sulfonylurea sorafenib analogs are worthy of further study. MDPI 2015-10-23 /pmc/articles/PMC6332012/ /pubmed/26512636 http://dx.doi.org/10.3390/molecules201019361 Text en © 2015 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 license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wu, Chunjiang Wang, Min Tang, Qidong Luo, Rong Chen, Le Zheng, Pengwu Zhu, Wufu Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit |
title | Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit |
title_full | Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit |
title_fullStr | Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit |
title_full_unstemmed | Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit |
title_short | Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit |
title_sort | design, synthesis, activity and docking study of sorafenib analogs bearing sulfonylurea unit |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332012/ https://www.ncbi.nlm.nih.gov/pubmed/26512636 http://dx.doi.org/10.3390/molecules201019361 |
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