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New chromone derivatives bearing thiazolidine-2,4-dione moiety as potent PTP1B inhibitors: Synthesis and biological activity evaluation.
Zheng, Yingying; Lu, Li; Li, Mengyue; Xu, DeHua; Zhang, LaiShun; Xiong, Zhuang; Zhou, Yubo; Li, Jia; Xu, Xuetao; Zhang, Kun; Xu, Lei.
Afiliação
  • Zheng Y; Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China.
  • Lu L; Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China.
  • Li M; Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China.
  • Xu D; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 529199, PR China; School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, PR China.
  • Zhang L; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 529199, PR China; School of Pharmacy, Zunyi Medical University, Zunyi 563006, PR China.
  • Xiong Z; Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China.
  • Zhou Y; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 529199, PR China; National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR Chi
  • Li J; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 529199, PR China; National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR Chi
  • Xu X; Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China. Electronic address: wyuchemxxt@126.com.
  • Zhang K; Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, PR China. Electronic address: Kzhang@gdut.edu.cn.
  • Xu L; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 529199, PR China. Electronic address: 0024xl@zidd.ac.cn.
Bioorg Chem ; 143: 106985, 2024 Feb.
Article em En | MEDLINE | ID: mdl-38007892
A series of chromone derivatives bearing thiazolidine-2,4-dione moiety (5 âˆ¼ 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 âˆ¼ 16.83 ± 0.54 µM comparing to that of positive control lithocholic acid (IC50: 9.62 ± 0.14 µM). Among them, compound 9 had the strongest PTP1B inhibitory activity with the IC50 value of 1.40 ± 0.04 µM. 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tiazolidinedionas / Inibidores Enzimáticos / Proteína Tirosina Fosfatase não Receptora Tipo 1 Idioma: En Revista: Bioorg Chem Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tiazolidinedionas / Inibidores Enzimáticos / Proteína Tirosina Fosfatase não Receptora Tipo 1 Idioma: En Revista: Bioorg Chem Ano de publicação: 2024 Tipo de documento: Article