Synthesis, α-amylase and α-glucosidase inhibition and molecular docking studies of indazole derivatives

J Biomol Struct Dyn. 2022;40(21):10730-10740. doi: 10.1080/07391102.2021.1947892. Epub 2021 Aug 31.

Abstract

Herein, we report the synthesis and inhibitory potential of indazole (Methyl 1H-indazole-4-carboxylate) derivatives (1-13) against α-amylase and α-glucosidase enzymes. The described derivatives demonstrated good inhibitory potential with IC50 values, ranging between 15.04 ± 0.05 to 76.70 ± 0.06 µM ± SEM for α-amylase and 16.99 ± 0.19 to 77.97 ± 0.19 µM ± SEM for α-glucosidase, respectively. In particular, compounds (8-10 and 12) displayed significant inhibitory activities against both the screened enzymes, with their inhibitory potential comparable to the standard acarbose (12.98 ± 0.03 and 12.79 ± 0.17 µM ± SEM, respectively). Additionally, the influence of different substituents on enzyme inhibition activities was assessed to study the structure activity relationships. Molecular docking simulations were performed to rationalize the binding of derivatives/compounds with enzymes. All the synthesized derivatives (1-13) were characterized with the aid of spectroscopic instruments such as 1H-NMR, 13C-NMR, HR-MS, elemental analysis and FTIR.Communicated by Ramaswamy H. Sarma.

Keywords: FTIR; HR-MS; Indazole; NMR; molecular docking; spectral studies; α-amylase activity; α-glucosidase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glycoside Hydrolase Inhibitors / chemistry
  • Glycoside Hydrolase Inhibitors / pharmacology
  • Indazoles / pharmacology
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship
  • alpha-Amylases* / metabolism
  • alpha-Glucosidases* / chemistry

Substances

  • alpha-Glucosidases
  • alpha-Amylases
  • Glycoside Hydrolase Inhibitors
  • Indazoles