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Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation
A series of bromophenol hybrids with N-containing heterocyclic moieties were designed, and their anticancer activities against a panel of five human cancer cell lines (A549, Bel7402, HepG2, HCT116 and Caco2) using MTT assay in vitro were explored. Among them, thirteen compounds (17a, 17b, 18a, 19a,...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706033/ https://www.ncbi.nlm.nih.gov/pubmed/29104274 http://dx.doi.org/10.3390/md15110343 |
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author | Wang, Li-Jun Guo, Chuan-Long Li, Xiang-Qian Wang, Shuai-Yu Jiang, Bo Zhao, Yue Luo, Jiao Xu, Kuo Liu, Hua Guo, Shu-Ju Wu, Ning Shi, Da-Yong |
author_facet | Wang, Li-Jun Guo, Chuan-Long Li, Xiang-Qian Wang, Shuai-Yu Jiang, Bo Zhao, Yue Luo, Jiao Xu, Kuo Liu, Hua Guo, Shu-Ju Wu, Ning Shi, Da-Yong |
author_sort | Wang, Li-Jun |
collection | PubMed |
description | A series of bromophenol hybrids with N-containing heterocyclic moieties were designed, and their anticancer activities against a panel of five human cancer cell lines (A549, Bel7402, HepG2, HCT116 and Caco2) using MTT assay in vitro were explored. Among them, thirteen compounds (17a, 17b, 18a, 19a, 19b, 20a, 20b, 21a, 21b, 22a, 22b, 23a, and 23b) exhibited significant inhibitory activity against the tested cancer cell lines. The structure-activity relationships (SARs) of bromophenol derivatives were discussed. The promising candidate compound 17a could induce cell cycle arrest at G0/G1 phase and induce apoptosis in A549 cells, as well as caused DNA fragmentations, morphological changes and ROS generation by the mechanism studies. Furthermore, compound 17a suppression of Bcl-2 levels (decrease in the expression of the anti-apoptotic proteins Bcl-2 and down-regulation in the expression levels of Bcl-2) in A549 cells were observed, along with activation caspase-3 and PARP, which indicated that compound 17a induced A549 cells apoptosis in vitro through the ROS-mediated apoptotic pathway. These results might be useful for bromophenol derivatives to be explored and developed as novel anticancer drugs. |
format | Online Article Text |
id | pubmed-5706033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-57060332017-12-04 Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation Wang, Li-Jun Guo, Chuan-Long Li, Xiang-Qian Wang, Shuai-Yu Jiang, Bo Zhao, Yue Luo, Jiao Xu, Kuo Liu, Hua Guo, Shu-Ju Wu, Ning Shi, Da-Yong Mar Drugs Article A series of bromophenol hybrids with N-containing heterocyclic moieties were designed, and their anticancer activities against a panel of five human cancer cell lines (A549, Bel7402, HepG2, HCT116 and Caco2) using MTT assay in vitro were explored. Among them, thirteen compounds (17a, 17b, 18a, 19a, 19b, 20a, 20b, 21a, 21b, 22a, 22b, 23a, and 23b) exhibited significant inhibitory activity against the tested cancer cell lines. The structure-activity relationships (SARs) of bromophenol derivatives were discussed. The promising candidate compound 17a could induce cell cycle arrest at G0/G1 phase and induce apoptosis in A549 cells, as well as caused DNA fragmentations, morphological changes and ROS generation by the mechanism studies. Furthermore, compound 17a suppression of Bcl-2 levels (decrease in the expression of the anti-apoptotic proteins Bcl-2 and down-regulation in the expression levels of Bcl-2) in A549 cells were observed, along with activation caspase-3 and PARP, which indicated that compound 17a induced A549 cells apoptosis in vitro through the ROS-mediated apoptotic pathway. These results might be useful for bromophenol derivatives to be explored and developed as novel anticancer drugs. MDPI 2017-11-01 /pmc/articles/PMC5706033/ /pubmed/29104274 http://dx.doi.org/10.3390/md15110343 Text en © 2017 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 Wang, Li-Jun Guo, Chuan-Long Li, Xiang-Qian Wang, Shuai-Yu Jiang, Bo Zhao, Yue Luo, Jiao Xu, Kuo Liu, Hua Guo, Shu-Ju Wu, Ning Shi, Da-Yong Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation |
title | Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation |
title_full | Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation |
title_fullStr | Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation |
title_full_unstemmed | Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation |
title_short | Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation |
title_sort | discovery of novel bromophenol hybrids as potential anticancer agents through the ros-mediated apoptotic pathway: design, synthesis and biological evaluation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706033/ https://www.ncbi.nlm.nih.gov/pubmed/29104274 http://dx.doi.org/10.3390/md15110343 |
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