Design, synthesis and antitumor evaluation of novel 1H-indole-2-carboxylic acid derivatives targeting 14-3-3η protein

doi:10.1016/j.ejmech.2022.114402

Residential College	false
Status	已發表Published
	Design, synthesis and antitumor evaluation of novel 1H-indole-2-carboxylic acid derivatives targeting 14-3-3η protein
	Gao, Zhenxiong 1,2; Fan, Tingting 2,3; Chen, Linbo 2,3; Yang, Mengchu 4; Wai Wong, Vincent Kam 4; Chen, Dawei 5,6; Liu, Zijian 5,6; Zhou, Yaoyao 2; Wu, Weibin 5,6; Qiu, Zixuan 2; Zhang, Cunlong 5,6,10; Li, Yuan 7; Jiang, Yuyang 2,3,8,9
	2022-08-05
Source Publication	European Journal of Medicinal Chemistry
ISSN	0223-5234
Volume	238
Abstract	In this work, a series of novel 1H-indole-2-carboxylic acid derivatives targeting 14-3-3η protein were designed and synthesized for treatment of liver cancer. After structural optimization for several rounds, C11 displayed a relatively better affinity with 14-3-3η, as well as the best inhibitory activities against several typical human liver cancer cell lines, including Bel-7402, SMMC-7721, SNU-387, Hep G2 and Hep 3B cells. Compound C11 also displayed best inhibitory activity against chemotherapy-resistant Bel-7402/5-Fu cells. Besides, C11 was rather safe against hERG and possessed moderate T and CL values in liver microsomes. In anti-proliferation, trans-well and cell apoptosis assays, C11 also showed its huge potential as a potent antitumor agent. Then, Western blot assay was conducted, following analyzed by molecular docking, the anti-proliferative mechanisms of this small-molecule inhibitor were revealed. Moreover, C11 was demonstrated to induce G-S phase cell cycle arrest in liver cancer cells.
Keyword	14-3-3η Protein Antitumor Bioactivity Drug Design Hepatocellular Carcinoma Novel Target
DOI	10.1016/j.ejmech.2022.114402
URL	View the original
Indexed By	SCIE ; IC
Language	英語English
WOS Research Area	Pharmacology & Pharmacy
WOS Subject	Chemistry, Medicinal
WOS ID	WOS:000804189700004
Publisher	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 65 RUE CAMILLE DESMOULINS, CS50083, 92442 ISSY-LES-MOULINEAUX, FRANCE
Scopus ID	2-s2.0-85129280207
Fulltext Access	View Full-Text via DOI View Full-Text via Web of Science View Full-Text via Scopus
Citation statistics
Document Type	Journal article
Collection	University of Macau
Corresponding Author	Zhang, Cunlong; Li, Yuan; Jiang, Yuyang
Affiliation	1.Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China 2.State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China 3.Department of Chemistry Southern University of Science and Technology, Shenzhen, 518055, China 4.Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China 5.Shenzhen Kivita Innovat Drug Discovery Inst, Shenzhen, 518057, China 6.Shenzhen Bay Bio-pharm Technology Co., Ltd, Shenzhen, 518057, China 7.The Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China 8.Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China 9.Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China 10.Shenzhen Bay Biopharm Technol Co Ltd, Shenzhen Kivita Innovat Drug Discovery Inst, Shenzhen 518057, Peoples R China
Recommended Citation GB/T 7714	Gao, Zhenxiong,Fan, Tingting,Chen, Linbo,et al. Design, synthesis and antitumor evaluation of novel 1H-indole-2-carboxylic acid derivatives targeting 14-3-3η protein[J]. European Journal of Medicinal Chemistry, 2022, 238.
APA	Gao, Zhenxiong., Fan, Tingting., Chen, Linbo., Yang, Mengchu., Wai Wong, Vincent Kam., Chen, Dawei., Liu, Zijian., Zhou, Yaoyao., Wu, Weibin., Qiu, Zixuan., Zhang, Cunlong., Li, Yuan., & Jiang, Yuyang (2022). Design, synthesis and antitumor evaluation of novel 1H-indole-2-carboxylic acid derivatives targeting 14-3-3η protein. European Journal of Medicinal Chemistry, 238.
MLA	Gao, Zhenxiong,et al."Design, synthesis and antitumor evaluation of novel 1H-indole-2-carboxylic acid derivatives targeting 14-3-3η protein".European Journal of Medicinal Chemistry 238(2022).

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