Diphenyl-substituted triazine derivatives: synthesis, α-glucosidase inhibitory activity, kinetics and in silico studies

Future Med Chem. 2023 Sep;15(18):1651-1668. doi: 10.4155/fmc-2023-0057. Epub 2023 Sep 20.

Abstract

Background: Diabetes mellitus (DM) is a chronic disorder, considered to be a major global health challenge in the 21st century. α-Glucosidase enzyme is a well-known drug target to treat Type II DM. Methods: A new library of biphenyl-substituted triazines was synthesized and confirmed by various spectroscopic techniques. Results: All compounds showed potent α-glucosidase inhibitory activity, with IC50 values ranging from 35.35 ± 0.34 to 564.41 ± 0.91 μM, as the standard acarbose, IC50 value of 750.7 ± 0.13 μM. Our in silico study has predicted key interactions with the enzyme's active site. Drug-likeness and absorption, distribution, metabolism, excretion and toxicity were also studied. Conclusion: This study has identified a range of potential hits against the α-glucosidase enzyme that may serve as antidiabetic agents after further investigations.

Keywords: competitive inhibitor; diabetes mellitus; in silico studies; triazine; α-glucosidase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glycoside Hydrolase Inhibitors* / chemistry
  • Hypoglycemic Agents / chemistry
  • Kinetics
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship
  • Triazines / chemistry
  • Triazines / pharmacology
  • alpha-Glucosidases* / metabolism

Substances

  • diphenyl
  • Glycoside Hydrolase Inhibitors
  • alpha-Glucosidases
  • Hypoglycemic Agents
  • Triazines