In vitro α-Glucosidase Inhibition by Non-sugar based Triazoles of Dibenzoazepine, their Structure-Activity Relationship, and Molecular Docking

Med Chem. 2017;13(7):698-704. doi: 10.2174/1573406413666170726142949.

Abstract

Background: α-Glucosidase inhibitors (AGIs) have been reported for their clinical potential against postprandial hyperglycemia, which is responsible for the risks associated with diabetes mellitus 2 and cardiovascular diseases (CVDs). Besides, a number of compounds have been reported as potent AGIs, several side effects are associated with them.

Methods: The aim of present work is to explore new and potent molecules as AGIs. Therefore, a library of dibenzoazepine linked triazoles (1-15) was studied for their in vitro α-glucosidase inhibitory activity. The binding modes of potent compounds in the active site of α-glucosidase enzyme were also explored through molecular docking studies.

Results and conclusion: Among the reported triazoles, compounds 3-9, 11, and 13 (IC50 = 6.0 ± 0.03 to 19.8 ± 0.28 µM) were found to be several fold more active than the standard drug acarbose (IC50 = 840 ± 1.73 µM). Compound 5 (IC50 = 6.0 ± 0.03 µM) was the most potent AGIs in the series, about 77- fold more active than acarbose. Therefore, dibenzoazepine linked-triazoles described here can serve as leads for further studies as new non-sugar AGIs.

Keywords: Acetophenones; diabetes; dibenzoazepine; molecular docking; triazoles; α-glucosidase.

MeSH terms

  • Acarbose / pharmacology
  • Catalytic Domain
  • Dibenzazepines / chemical synthesis
  • Dibenzazepines / pharmacology*
  • Glycoside Hydrolase Inhibitors / chemical synthesis
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Molecular Docking Simulation
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / pharmacology*
  • alpha-Glucosidases / metabolism*

Substances

  • Dibenzazepines
  • Glycoside Hydrolase Inhibitors
  • Triazoles
  • alpha-Glucosidases
  • Acarbose