Synthesis, characterization, antidiabetic and antioxidative evaluation of a novel Zn(II)-gallic acid complex with multi-facet activity

J Pharm Pharmacol. 2020 Oct;72(10):1412-1426. doi: 10.1111/jphp.13322. Epub 2020 Jul 8.

Abstract

Objectives: This study was done to synthesize a novel Zn(II)-gallic acid complex with improved antidiabetic and antioxidative properties.

Methods: The complex was synthesized and characterized using Fourier Transform Infrared (FT-IR) and 1 H NMR. Cytotoxicity was evaluated using Chang liver cells and L6 myotubes. Radical scavenging and Fe3+ -reducing, as well as α-glucosidase, α-amylase and glycation inhibitory properties were measured. Glucose uptake was measured in L6 myotubes, while the complex was docked against glucose transporter type 4 (GLUT-4) and protein kinase B (PKB).

Key findings: Analysis showed that complexation occurred through a Zn(O4 ) coordination; thus, the complex acquired two moieties of gallic acid, which suggests why complexation increased the DPPH (IC50 = 48.2 µm) and ABTS (IC50 = 12.7 µm) scavenging and α-glucosidase inhibitory (IC50 = 58.5 µm) properties of gallic acid by several folds (5.5, 3.6 and 2.7 folds; IC50 = 8.79, 3.51 and 21.5 µm, respectively). Zn(II) conferred a potent dose-dependent glucose uptake activity (EC50 = 9.17 µm) on gallic acid, without reducing the viability of L6 myotubes and hepatocytes. Docking analysis showed the complex had stronger interaction with insulin signalling proteins (GLUT-4 and PKB) than its precursor.

Conclusions: Data suggest that complexation of Zn(II) with gallic acid resulted in a complex with improved and multi-facet antioxidative and glycaemic control properties.

Keywords: Zn(II) complex; diabetes; gallic acid; glucose uptake; zinc(II) acetate.

MeSH terms

  • Antioxidants / chemical synthesis*
  • Antioxidants / pharmacology
  • Cell Line
  • Drug Evaluation, Preclinical / methods
  • Gallic Acid / chemical synthesis*
  • Gallic Acid / pharmacology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / pharmacology
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Spectroscopy, Fourier Transform Infrared / methods
  • Zinc / chemistry*
  • Zinc / pharmacology

Substances

  • Antioxidants
  • Hypoglycemic Agents
  • Gallic Acid
  • Zinc