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New chromone derivatives bearing thiazolidine-2,4-dione moiety as potent PTP1B inhibitors: Synthesis and biological activity evaluation

文献类型：期刊论文

作者Zheng, Yingying5; Lu, Li5; Li, Mengyue5; Xu, Dehua3,4; Zhang, Laishun2; Xiong, Zhuang5; Zhou, Yubo1; Li, Jia1; Xu, Xuetao5; Zhang, Kun5
刊名BIOORGANIC CHEMISTRY
出版日期2024-02-01
卷号143页码:9
ISSN号0045-2068
关键词Chromone Thiazolidine-2 4-dione Protein tyrosine phosphatase 1B Inhibitors
DOI10.1016/j.bioorg.2023.106985
通讯作者Xu, Xuetao(wyuchemxxt@126.com) ; Zhang, Kun(Kzhang@gdut.edu.cn) ; Xu, Lei(0024xl@zidd.ac.cn)
英文摘要A series of chromone derivatives bearing thiazolidine-2,4-dione moiety (5 similar to 37) were synthesized and evaluated for their PTP1B inhibitory activity, interaction analysis and effects on insulin pathway in palmitic acid (PA)-induced HepG2 cells. The results showed that all derivatives presented potential PTP1B inhibitory activity with IC50 values of 1.40 +/- 0.04 similar to 16.83 +/- 0.54 mu M comparing to that of positive control lithocholic acid (IC50: 9.62 +/- 0.14 mu M). Among them, compound 9 had the strongest PTP1B inhibitory activity with the IC50 value of 1.40 +/- 0.04 mu M. Inhibition kinetic study revealed that compound 9 was a reversible mixed-type inhibitor against PTP1B. CD spectra results confirmed that compound 9 changed the secondary structure of PTP1B by their interaction. Molecular docking explained the detailed binding between compound 9 and PTP1B. Compound 9 also showed 19-fold of selectivity for PTP1B over TCPTP. Moreover compound 9 could recovery PA-induced insulin resistance by increasing the phosphorylation of IRSI and AKT. CETSA results showed that compound 9 significantly increased the thermal stability of PTP1B.
WOS关键词TYROSINE-PHOSPHATASE 1B ; ANTIDIABETIC AGENTS ; NEGATIVE REGULATOR ; DESIGN ; DISCOVERY ; INSULIN ; AMIDES
资助项目Department of Education of Guangdong Province[2021KCXTD044] ; Science and Technology Planning Project of Guangdong Province[2021B1212040016] ; Joint Research Fund for Wuyi University and Hong Kong and Macao[2021WGALH08] ; Key Project of Jiangmen Basic and Applied Basic Research[2021030103150006664]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号WOS:001127773900001
源URL[http://119.78.100.183/handle/2S10ELR8/308329]  
专题新药研究国家重点实验室
通讯作者Xu, Xuetao; Zhang, Kun; Xu, Lei
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Zunyi Med Univ, Sch Pharm, Zunyi 563006, Peoples R China
3.Dalian Univ Technol, Sch Life & Pharmaceut Sci, Panjin, Peoples R China
4.Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Chinese Acad Sci, Zhongshan 529199, Peoples R China
5.Wuyi Univ, Sch Pharm & Food Engn, Guangdong Prov Key Lab Large Anim Models Biomed, Jiangmen 529020, Peoples R China
推荐引用方式
GB/T 7714		 Zheng, Yingying,Lu, Li,Li, Mengyue,et al. New chromone derivatives bearing thiazolidine-2,4-dione moiety as potent PTP1B inhibitors: Synthesis and biological activity evaluation[J]. BIOORGANIC CHEMISTRY,2024,143:9.
APA Zheng, Yingying.,Lu, Li.,Li, Mengyue.,Xu, Dehua.,Zhang, Laishun.,...&Xu, Lei.(2024).New chromone derivatives bearing thiazolidine-2,4-dione moiety as potent PTP1B inhibitors: Synthesis and biological activity evaluation.BIOORGANIC CHEMISTRY,143,9.
MLA Zheng, Yingying,et al."New chromone derivatives bearing thiazolidine-2,4-dione moiety as potent PTP1B inhibitors: Synthesis and biological activity evaluation".BIOORGANIC CHEMISTRY 143(2024):9.

入库方式： OAI收割

来源：上海药物研究所

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