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Oleanolic acid indole derivatives as novel α-glucosidase inhibitors: Synthesis, biological evaluation, and mechanistic analysis.
Wu, Panpan; He, Hao; Ma, Hang; Tu, Borong; Li, Jiahao; Guo, Shengzhu; Chen, Silin; Cao, Nana; Zheng, Wende; Tang, Xiaowen; Li, Dongli; Xu, Xuetao; Zheng, Xi; Sheng, Zhaojun; David Hong, Weiqian; Zhang, Kun.
Afiliación
  • Wu P; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom.
  • He H; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China; Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Universit
  • Ma H; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
  • Tu B; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China.
  • Li J; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China.
  • Guo S; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China.
  • Chen S; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China.
  • Cao N; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China.
  • Zheng W; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China.
  • Tang X; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China.
  • Li D; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China.
  • Xu X; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China.
  • Zheng X; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China.
  • Sheng Z; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China. Electronic address: wyuchemszj@126.com.
  • David Hong W; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom. Electronic address: davidhwq@liverpool.a
  • Zhang K; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529040, PR China. Electronic address: kzhang@gdut.edu.cn.
Bioorg Chem ; 107: 104580, 2021 02.
Article en En | MEDLINE | ID: mdl-33418317
Research efforts have been directed to the development of oleanolic acid (OA) based α-glucosidase inhibitors and various OA derivatives showed improved anti-α-glucosidase activity. However, the inhibitory effects of indole infused OA derivatives on α-glucosidase is unknown. Herein, we synthesized a series of indole-OA (2a-2o) and -OA methyl ester (3a-3 l) derivatives with various electron withdrawing groups inducted to indole benzene ring and evaluated their anti-α-glucosidase activity. Indole OA derivatives (2a-2o) exhibited superior α-glucosidase inhibitory effects as compared to OA methyl ester derivatives (3a-3l) and OA (with IC50 values of 4.02 µM-5.30 µM v.s. over 10 µM and 5.52 µM, respectively). In addition, mechanistic studies using biochemical (kinetic assay), biophysical (circular dichroism), and computational (docking) methods revealed that OA-indole derivatives (2a and 2f) are mixed type of α-glucosidase inhibitors and their inhibitory effects were attributed to their capacity of forming the ligand-enzyme complex with α-glucosidase enzyme. Findings from this study support that OA indole derivatives are promising α-glucosidase inhibitors as a potential management of diabetes mellitus.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Oleanólico / Alfa-Glucosidasas / Inhibidores de Glicósido Hidrolasas Idioma: En Revista: Bioorg Chem Año: 2021 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Oleanólico / Alfa-Glucosidasas / Inhibidores de Glicósido Hidrolasas Idioma: En Revista: Bioorg Chem Año: 2021 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos