2. Academic Validation
  3. Synthesis and biological evaluation of coumarin derivatives as α-glucosidase inhibitors

Synthesis and biological evaluation of coumarin derivatives as α-glucosidase inhibitors

  • Eur J Med Chem. 2020 Mar 1;189:112013. doi: 10.1016/j.ejmech.2019.112013.
Xue-Tao Xu 1,  Xu-Yang Deng 1,  Jie Chen 1,  Qi-Ming Liang 1,  Kun Zhang 1,  Dong-Li Li 1,  Pan-Pan Wu 1,  Xi Zheng 2,  Ren-Ping Zhou 2,  Zheng-Yun Jiang 2,  Ai-Jun Ma 3,  Wen-Hua Chen 4,  Shao-Hua Wang 5
Affiliations

Affiliations

  • 1 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529020, PR China.
  • 2 Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
  • 3 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529020, PR China. Electronic address: [email protected].
  • 4 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529020, PR China. Electronic address: [email protected].
  • 5 School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, PR China; International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529020, PR China; School of Pharmacy & State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, 730000, PR China. Electronic address: [email protected].
PMID: 31972390 DOI: 10.1016/j.ejmech.2019.112013
Abstract

In this study, two series of coumarin derivatives 5a∼i and 6a∼i were synthesized, and their inhibitory activity against α-glucosidase was determined. The results indicated that most of the synthesized derivatives exhibited prominent inhibitory activities against α-glucosidase. Among them, compounds 5a and 5b showed the strongest inhibition with the IC50 values of 19.64 μM and 12.98 μM, respectively. Enzyme kinetic studies of compounds 5a and 5b proved that their inhibition was reversible and a mixed type. The KI and KIS values of compound 5a were calculated to be 27.39 μM and 13.02 μM, respectively, and the corresponding values for compound 5b being 27.02 μM and 13.65 μM, respectively. The docking studies showed that compound 5b could be inserted into the active pocket of α-glucosidase and form hydrogen bonds with LYS293 to enhance the binding affinity.

Keywords

Cinnamic acid; Coumarin; Enzyme inhibition; Molecular docking; Synthesis; α-Glucosidase.

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