Design and synthesis of new imidazo[1,2-b]pyrazole derivatives, in vitro α-glucosidase inhibition, kinetic and docking studies

Mol Divers. 2020 Feb;24(1):69-80. doi: 10.1007/s11030-019-09925-8. Epub 2019 Mar 2.

Abstract

A new series of imidazo[1,2-b]pyrazole derivatives 4a-o was designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity. All compounds showed high inhibitory activity in the range of IC50 = 95.0 ± 0.5-372.8 ± 1.0 µM as compared to standard drug acarbose (IC50 = 750 ± 1.5 µM) and were also found to be non-cytotoxic. Among the synthesized compounds, the most potent compound was compound 4j with eightfold higher inhibitory activity compared to acarbose. Like acarbose, compound 4j inhibited α-glucosidase in a competitive mode. Molecular modeling studies of the most potent compounds 4j, 4f, 4o, and 4c were also conducted.

Keywords: Docking study; Imidazo[1,2-b]pyrazole; Imidazole; Pyrazole; α-Glucosidase.

MeSH terms

  • Binding Sites
  • Chemistry Techniques, Synthetic*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Activation
  • Glycoside Hydrolase Inhibitors / chemical synthesis
  • Glycoside Hydrolase Inhibitors / chemistry*
  • Glycoside Hydrolase Inhibitors / pharmacology
  • Kinetics
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • Molecular Structure
  • Protein Binding
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology
  • Structure-Activity Relationship
  • alpha-Glucosidases / chemistry*

Substances

  • Glycoside Hydrolase Inhibitors
  • Pyrazoles
  • imidazopyrazole
  • alpha-Glucosidases