S3I-201 derivative incorporating naphthoquinone unit as effective STAT3 inhibitors: Design, synthesis and anti-gastric cancer evaluation

doi:10.1016/j.bmc.2022.116941

	S3I-201 derivative incorporating naphthoquinone unit as effective STAT3 inhibitors: Design, synthesis and anti-gastric cancer evaluation
	Li, Haobin 1; Cai, Maohua 1; Cao, Fei 2; Yu, Dehua 1; Yang, Jing 1; Yu, Wenkai 1; Chu, Chu 2; Guan, Xiaoqing 3,4; Qin, Jiang-Jiang 1,3,4; Dong, Jinyun 1,3,4
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2022-10-01
卷号	71
关键词	STAT3 inhibitor Quinone derivative S3I-201 Anti -gastric cancer drug
ISSN号	0968-0896
DOI	10.1016/j.bmc.2022.116941
通讯作者	Qin, Jiang-Jiang(jqin@ucas.ac.cn) ; Dong, Jinyun(dongjy@ibmc.ac.cn)
英文摘要	Signal transducer and activator of transcription 3 (STAT3) is a key regulator of many human cancers and has been widely recognized as a promising target for cancer therapy. A variety of small-molecule inhibitors have been developed for targeting STAT3, and some of them are now undergoing clinical trials. S3I-201, a known STAT3 inhibitor, may block STAT3 function in cancer cells by binding to the STAT3 SH2 domain to disrupt STAT3 protein complex formation. Using S3I-201 as a starting point for drug development, we synthesized a series of new STAT3 inhibitors 9a-x in this study by introducing naphthoquinone unit, a privileged fragment in STAT3 inhibitors. Most of the compounds exhibited strong anti-proliferation activity of gastric cancer cells (MGC803, MKN28, MNK1, and AGS). The representative compound 9n (SIL-14) could effectively inhibit the colony formation and migration of gastric cancer cells MGC803, arrest the cell cycle and induce MGC803 cell apoptosis at low micromolar concentrations in vitro. In addition, SIL-14 can also inhibit the phosphorylation of STAT3 protein and significantly decrease the expression of total STAT3, suggesting that it may exert anticancer effects by blocking the STAT3 signaling pathway. These results support that SIL-14 may be a promising STAT3 inhibitor for the further development of potential anti-gastric cancer candidates.
资助项目	Zhejiang Provincial Natural Science Foundation of China[LQ21B020003] ; National Natural Science Foundation of China[82103967] ; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province[2022E10021] ; Program of Zhejiang Provincial TCM Sci-tech Plan[2020ZZ005]
WOS关键词	SIGNAL TRANSDUCER ; TRANSCRIPTION ; DISCOVERY ; ACTIVATOR ; ACID
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000860419100002
资助机构	Zhejiang Provincial Natural Science Foundation of China ; National Natural Science Foundation of China ; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province ; Program of Zhejiang Provincial TCM Sci-tech Plan
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/129173]
专题	中国科学院合肥物质科学研究院
通讯作者	Qin, Jiang-Jiang; Dong, Jinyun
作者单位	1.Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 310053, Peoples R China 2.Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310032, Peoples R China 3.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou 310018, Zhejiang, Peoples R China 4.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Li, Haobin,Cai, Maohua,Cao, Fei,et al. S3I-201 derivative incorporating naphthoquinone unit as effective STAT3 inhibitors: Design, synthesis and anti-gastric cancer evaluation[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2022,71.
APA	Li, Haobin.,Cai, Maohua.,Cao, Fei.,Yu, Dehua.,Yang, Jing.,...&Dong, Jinyun.(2022).S3I-201 derivative incorporating naphthoquinone unit as effective STAT3 inhibitors: Design, synthesis and anti-gastric cancer evaluation.BIOORGANIC & MEDICINAL CHEMISTRY,71.
MLA	Li, Haobin,et al."S3I-201 derivative incorporating naphthoquinone unit as effective STAT3 inhibitors: Design, synthesis and anti-gastric cancer evaluation".BIOORGANIC & MEDICINAL CHEMISTRY 71(2022).