Novel pyridine-2,4,6-tricarbohydrazide thiourea compounds as small key organic molecules for the potential treatment of type-2 diabetes mellitus: In vitro studies against yeast α- and β-glucosidase and in silico molecular modeling

Arch Pharm (Weinheim). 2018 Jan;351(1). doi: 10.1002/ardp.201700236. Epub 2017 Dec 1.

Abstract

A range of novel pyridine-2,4,6-tricarbohydrazide thiourea compounds (4a-i) were synthesized in good to excellent yields (63-92%). The enzyme inhibitory potentials of these compounds were investigated against α- and β-glucosidases because these enzymes play a crucial role in treating type-2 diabetes mellitus (T2DM). As compared to the reference compound acarbose (IC50 38.22 ± 0.12 μM), compounds 4i (IC50 25.49 ± 0.67 μM), 4f (IC50 28.91 ± 0.43 μM), 4h (IC50 30.66 ± 0.52 μM), and 4e (IC50 35.01 ± 0.45 μM) delivered better inhibition against α-glucosidase and were quite inactive/completely inactive against β-glucosidase. The structure-activity relationship of these compounds was developed and elaborated with the help of molecular docking studies.

Keywords: 2,4,6-tricarbohydrazide; acarbose; diabetes mellitus type-2; pyridine derivatives; thiourea; α-glucosidase.

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Glycoside Hydrolase Inhibitors / chemical synthesis
  • Glycoside Hydrolase Inhibitors / chemistry
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Molecular Docking Simulation
  • Molecular Structure
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Saccharomyces cerevisiae / enzymology
  • Structure-Activity Relationship
  • Thiourea / analogs & derivatives*
  • Thiourea / chemical synthesis
  • Thiourea / chemistry
  • Thiourea / pharmacology*
  • alpha-Glucosidases / metabolism*
  • beta-Glucosidase / antagonists & inhibitors*
  • beta-Glucosidase / metabolism

Substances

  • Glycoside Hydrolase Inhibitors
  • Pyridines
  • alpha-Glucosidases
  • beta-Glucosidase
  • Thiourea