Synthesis of 6-chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives: Antidiabetic, antioxidant, β-glucuronidase inhibiton and their molecular docking studies

Bioorg Chem. 2016 Apr:65:48-56. doi: 10.1016/j.bioorg.2016.01.007. Epub 2016 Feb 1.

Abstract

6-Chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives 1-26 were synthesized and characterized by various spectroscopic techniques. All these derivatives were evaluated for their antiglycation, antioxidant and β-glucuronidase potential followed their docking studies. In antiglycation assay, compound 2 (IC50=240.10±2.50μM) and 4 (IC50=240.30±2.90μM) was found to be most active compound of this series, while compounds 3 (IC50=260.10±2.50μM), 6 (IC50=290.60±3.60μM), 13 (IC50=288.20±3.00μM) and 26 (IC50=292.10±3.20μM) also showed better activities than the standard rutin (IC50=294.50±1.50μM). In antioxidant assay, compound 1 (IC50=69.45±0.25μM), 2 (IC50=58.10±2.50μM), 3 (IC50=74.25±1.10μM), and 4 (IC50=72.50±3.30μM) showed good activities. In β-glucuronidase activity, compounds 3 (IC50=29.25±0.50μM), compound 1 (IC50=30.10±0.60μM) and compound 4 (IC50=46.10±1.10μM) showed a significant activity as compared to than standard D-Saccharic acid 1,4-lactonec (IC50=48.50±1.25μM) and their interaction with the enzyme was confirm by docking studies.

Keywords: 6-Chloro-2-Aryl-1H-imidazo[4, 5-b]pyridine; Anti-oxidant; Antiglycation; Spectroscopy; β-Glucuronidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Glucuronidase / antagonists & inhibitors*
  • Glucuronidase / metabolism
  • Glycoproteins / chemical synthesis
  • Glycoproteins / chemistry
  • Glycoproteins / pharmacology*
  • Humans
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Molecular Docking Simulation*
  • Molecular Structure
  • Purines / chemical synthesis*
  • Purines / chemistry
  • Purines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Glycoproteins
  • Hypoglycemic Agents
  • Purines
  • beta-glucuronidase inhibitor
  • 1H-imidazo(4,5-b)pyridine
  • Glucuronidase