Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents

doi:10.3389/fchem.2024.1384301

科研成果详情

题名	Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents
作者	Xu, Xuemei 1; Zhu, Zhaojingtao2; Chen, Siyu 2; Fu, Yanneng2; Zhang, Jinxia2; Guo, Yangyang2; Xu, Zhouyang2; Xi, Yingying2; Wang, Xuebao 2; Ye, Faqing2; Chen, Huijun 3; Yang, Xiaojiao4
发表日期	2024-03-18
发表期刊	FRONTIERS IN CHEMISTRY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	organic synthesis benzothiazole derivatives anticancer antiinflammatory biological evaluation
其他关键词	CELLS
摘要	Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks.Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-alpha in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers.Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-alpha, and hindered cell migration. In addition, at concentrations of 1, 2, and 4 mu M, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6-dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties.Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-alpha. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study's mechanistic exploration, highlighting B7's simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression.
资助项目	Basic social development science and technology projects of Wenzhou [Y20210214, Y20220206]; Basic social development science and technology projects of Taizhou [20ywb67]; Scientific research projects of Zhejiang Provincial Education Department [Y202249707]
出版者	FRONTIERS MEDIA SA
ISSN	2296-2646
卷号	12
DOI	10.3389/fchem.2024.1384301
页数	17
WOS类目	Chemistry, Multidisciplinary
WOS研究方向	Chemistry
WOS记录号	WOS:001194515400001
收录类别	SCIE ; SCOPUS
URL	查看原文
PubMed ID	38562527
SCOPUSEID	2-s2.0-85189135083
通讯作者地址	[Ye, Faqing]School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China ; [Chen, Huijun]Department of Pharmacy,The First People’s Hospital of Taizhou,Taizhou,China ; [Yang, Xiaojiao]Scientific Research Center,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Chemistry (all)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/210986
专题	药学院（分析测试中心）附属第二医院_科研中心
通讯作者	Ye, Faqing; Chen, Huijun; Yang, Xiaojiao
作者单位	1.Department of Pharmacy,Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine,Wenzhou,China; 2.School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,China; 3.Department of Pharmacy,The First People’s Hospital of Taizhou,Taizhou,China; 4.Scientific Research Center,Wenzhou Medical University,Wenzhou,China
通讯作者单位	温州医科大学
推荐引用方式 GB/T 7714	Xu, Xuemei,Zhu, Zhaojingtao,Chen, Siyu,et al. Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents[J]. FRONTIERS IN CHEMISTRY,2024,12.
APA	Xu, Xuemei., Zhu, Zhaojingtao., Chen, Siyu., Fu, Yanneng., Zhang, Jinxia., ... & Yang, Xiaojiao. (2024). Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents. FRONTIERS IN CHEMISTRY, 12.
MLA	Xu, Xuemei,et al."Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents".FRONTIERS IN CHEMISTRY 12(2024).