Design, synthesis and biological evaluation of indoline-maleimide conjugates as potential antitumor agents for the treatment of colorectal cancer

doi:10.1016/j.bmc.2024.117786

科研成果详情

题名	Design, synthesis and biological evaluation of indoline-maleimide conjugates as potential antitumor agents for the treatment of colorectal cancer
作者	Tang, Jielin2; Zhang, Yuxin2; Zhou, Lingling2; Song, Xiangrui2; Wei, Yusi3,4; Qi, Ji3,4; Wu, Jianmin3,4; Song, Zengqiang2; Zhan, Lingling1
发表日期	2024-06-15
发表期刊	Bioorganic and Medicinal Chemistry 影响因子和分区
语种	英语
原始文献类型	Article
关键词	AKT/GSK-3β Antitumor Colorectal cancer Efficient synthesis Indoline-maleimide conjugates
其他关键词	INHIBITORS ; PATHWAY ; BREAST
摘要	An efficient protocol for direct coupling of maleimides and indolines at the C7-position was achieved under Rh(III) catalysis. Thirty four novel indoline-maleimide conjugates were prepared in good to excellent yields using this method. All compounds were evaluated for their anti-proliferative effect against colorectal cell lines. Among them, compound 3ab showed the most potent anti-proliferative activity against the CRC cells, and displayed low toxicity in the normal cell. Further investigation indicated that 3ab could effectively suppress the proliferation and migration of CRC cells, along with inducing cell cycle arrest and apoptosis. Mechanistic studies revealed that compound 3ab inhibited the proliferation of CRC cells via suppressing the AKT/GSK-3β pathway. In vivo evaluation demonstrated remarkable antitumor effect of 3ab (10 mg/kg) in the HCT116 xenograft model with no obvious toxicity, which is superior to that of 5-Fluorouracil (20 mg/kg). Therefore, conjugate 3ab could be considered as a potential CRC therapy agent for further development.
资助项目	National Natural Science Foundation of China[22077096];Natural Science Foundation of Zhejiang Province[LY23B020006];Wenzhou Municipal Science & Technology Bureau[Y20220128]
出版者	Elsevier Ltd
ISSN	0968-0896
EISSN	1464-3391
卷号	108
DOI	10.1016/j.bmc.2024.117786
页数	14
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
WOS记录号	WOS:001257481000001
收录类别	SCOPUS ; PUBMED ; SCIE
URL	查看原文
PubMed ID	38843656
SCOPUSEID	2-s2.0-85195071049
通讯作者地址	[Wu, Jianmin]Institute of Genomic Medicine,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Biochemistry;Molecular Medicine;Molecular Biology;Pharmaceutical Science;Drug Discovery;Clinical Biochemistry;Organic Chemistry
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/214957
专题	附属第一医院检验医学院（生命科学学院、生物学实验教学中心）药学院（分析测试中心）基因组医学研究院
通讯作者	Wu, Jianmin; Song, Zengqiang; Zhan, Lingling
作者单位	1.Department of Laboratory Medicine,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 3.Institute of Genomic Medicine,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 4.School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
第一作者单位	药学院（分析测试中心）
通讯作者单位	基因组医学研究院
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Tang, Jielin,Zhang, Yuxin,Zhou, Lingling,et al. Design, synthesis and biological evaluation of indoline-maleimide conjugates as potential antitumor agents for the treatment of colorectal cancer[J]. Bioorganic and Medicinal Chemistry,2024,108.
APA	Tang, Jielin., Zhang, Yuxin., Zhou, Lingling., Song, Xiangrui., Wei, Yusi., ... & Zhan, Lingling. (2024). Design, synthesis and biological evaluation of indoline-maleimide conjugates as potential antitumor agents for the treatment of colorectal cancer. Bioorganic and Medicinal Chemistry, 108.
MLA	Tang, Jielin,et al."Design, synthesis and biological evaluation of indoline-maleimide conjugates as potential antitumor agents for the treatment of colorectal cancer".Bioorganic and Medicinal Chemistry 108(2024).