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Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation

Authors :
Li-Jun Wang
Chuan-Long Guo
Xiang-Qian Li
Shuai-Yu Wang
Bo Jiang
Yue Zhao
Jiao Luo
Kuo Xu
Hua Liu
Shu-Ju Guo
Ning Wu
Da-Yong Shi
Source :
Marine Drugs, Vol 15, Iss 11, p 343 (2017)
Publication Year :
2017
Publisher :
MDPI AG, 2017.

Abstract

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.

Details

Language :
English
ISSN :
16603397
Volume :
15
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Marine Drugs
Publication Type :
Academic Journal
Accession number :
edsdoj.10d1a6beefa34e0782325febcf410c6e
Document Type :
article
Full Text :
https://doi.org/10.3390/md15110343