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

doi:10.3390/md15110343

IOCAS-IR > 实验海洋生物学重点实验室

	Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation
	Wang, Li-Jun 1,2; Guo, Chuan-Long 1,2,3; Li, Xiang-Qian 1,2; Wang, Shuai-Yu 1,2; Jiang, Bo 1,2; Zhao, Yue 1,2; Luo, Jiao 1,2,3; Xu, Kuo 1,2; Liu, Hua 1,2,3; Guo, Shu-Ju 1,2; Wu, Ning 1,2; Shi, Da-Yong 1,2,3
	2017-11-01
发表期刊	MARINE DRUGS
ISSN	1660-3397
卷号	15 期号:11 页码:18
通讯作者	Shi, Da-Yong(shidayong@qdio.ac.cn)
摘要	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.
关键词	bromophenol hybrids anticancer structure-activity relationships ROS apoptotic pathway
DOI	10.3390/md15110343
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[81773586] ; National Natural Science Foundation of China[81703354] ; Key research and development project of Shandong province[2016GSF201193] ; Key research and development project of Shandong province[2016ZDJS07A13] ; Key research and development project of Shandong province[2016GSF115002] ; Key research and development project of Shandong province[2016GSF115009] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-DQC014] ; Project of Discovery, Evaluation and Transformation of Active Natural Compounds, Strategic Biological Resources Service Network Programme of Chinese Academy of Sciences[ZSTH-026] ; NSFC-Shandong Joint Fund for Marine Science Rearch Centers[U1606403] ; Scientific and Technological Innovation Project - Qingdao National Laboratory for Marine Science and Technology[2015ASKJ02] ; AoShan Talents Program - Qingdao National Laboratory for Marine Science and Technology[2015ASTP] ; National Program for Support of Top-notch Young Professionals ; Taishan scholar Youth Project of Shandong province ; National Natural Science Foundation of China[81773586] ; National Natural Science Foundation of China[81703354] ; Key research and development project of Shandong province[2016GSF201193] ; Key research and development project of Shandong province[2016ZDJS07A13] ; Key research and development project of Shandong province[2016GSF115002] ; Key research and development project of Shandong province[2016GSF115009] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-DQC014] ; Project of Discovery, Evaluation and Transformation of Active Natural Compounds, Strategic Biological Resources Service Network Programme of Chinese Academy of Sciences[ZSTH-026] ; NSFC-Shandong Joint Fund for Marine Science Rearch Centers[U1606403] ; Scientific and Technological Innovation Project - Qingdao National Laboratory for Marine Science and Technology[2015ASKJ02] ; AoShan Talents Program - Qingdao National Laboratory for Marine Science and Technology[2015ASTP] ; National Program for Support of Top-notch Young Professionals ; Taishan scholar Youth Project of Shandong province ; National Natural Science Foundation of China[81773586] ; National Natural Science Foundation of China[81703354] ; Key research and development project of Shandong province[2016GSF201193] ; Key research and development project of Shandong province[2016ZDJS07A13] ; Key research and development project of Shandong province[2016GSF115002] ; Key research and development project of Shandong province[2016GSF115009] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-DQC014] ; Project of Discovery, Evaluation and Transformation of Active Natural Compounds, Strategic Biological Resources Service Network Programme of Chinese Academy of Sciences[ZSTH-026] ; NSFC-Shandong Joint Fund for Marine Science Rearch Centers[U1606403] ; Scientific and Technological Innovation Project - Qingdao National Laboratory for Marine Science and Technology[2015ASKJ02] ; Aoshan Talents Program - Qingdao National Laboratory for Marine Science and Technology[2015ASTP] ; National Program for Support of Top-notch Young Professionals ; Taishan scholar Youth Project of Shandong province
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000416600200014
出版者	MDPI AG
引用统计	被引频次：24[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/157294
专题	实验海洋生物学重点实验室
通讯作者	Shi, Da-Yong
作者单位	1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Shandong, Peoples R China 2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao 266071, Shandong, Peoples R China 3.Univ Chinese Acad Sci, Beijing 10049, Peoples R China
第一作者单位	中国科学院海洋研究所
通讯作者单位	中国科学院海洋研究所
推荐引用方式 GB/T 7714	Wang, Li-Jun,Guo, Chuan-Long,Li, Xiang-Qian,et al. Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation[J]. MARINE DRUGS,2017,15(11):18.
APA	Wang, Li-Jun.,Guo, Chuan-Long.,Li, Xiang-Qian.,Wang, Shuai-Yu.,Jiang, Bo.,...&Shi, Da-Yong.(2017).Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation.MARINE DRUGS,15(11),18.
MLA	Wang, Li-Jun,et al."Discovery of Novel Bromophenol Hybrids as Potential Anticancer Agents through the Ros-Mediated Apoptotic Pathway: Design, Synthesis and Biological Evaluation".MARINE DRUGS 15.11(2017):18.