Evaluation and molecular modelling of bis-Schiff base derivatives as potential leads for management of diabetes mellitus

Acta Pharm. 2022 Apr 13;72(3):449-458. doi: 10.2478/acph-2022-0019. Print 2022 Sep 1.

Abstract

Developing a medication to cure and manage diabetes mellitus complications is of interest in medicinal chemistry. Toward this end, six bis-biphenyl-salicylaldehyde Schiff base derivatives have been evaluated for their α-glucosidase inhibition, antiglycation and anti-inflammation potentials. Four compounds (compounds 2-5) showed an excellent α-glucosidase inhibitory effect superior to that produced by acarbose. Additionally, the docking study revealed that these compounds are anchored within the binding pocket of α-glucosidase via hydrogen bonding, π-stacking and hydrophobic interactions, comparable to a high number of hydrogen bonding involved in anchoring acarbose. Interestingly, all tested compounds showed varying degrees of antiglycation activity with superior activity for two of them (compound 1 and compound 6) compared to the standard rutin. Moreover, the results indicated an outstanding anti-inflammatory activity for two compounds (compounds 1 and 6) compared to ibuprofen.

Keywords: bis-Schiff bases; diabetes mellitus; docking study; glycation; postprandial hyperglycemia; α-glucosidase.

MeSH terms

  • Acarbose*
  • Diabetes Mellitus*
  • Glycoside Hydrolase Inhibitors / chemistry
  • Glycoside Hydrolase Inhibitors / metabolism
  • Glycoside Hydrolase Inhibitors / pharmacology
  • Humans
  • Molecular Docking Simulation
  • Schiff Bases / chemistry
  • Schiff Bases / pharmacology
  • Structure-Activity Relationship
  • alpha-Glucosidases / metabolism

Substances

  • Acarbose
  • alpha-Glucosidases
  • Glycoside Hydrolase Inhibitors
  • Schiff Bases