Synthesis of diindolylmethane (DIM) bearing thiadiazole derivatives as a potent urease inhibitor

Sci Rep. 2020 May 14;10(1):7969. doi: 10.1038/s41598-020-64729-3.

Abstract

The current study describes synthesis of diindolylmethane (DIM) derivatives based-thiadiazole as a new class of urease inhibitors. Diindolylmethane is natural product alkaloid reported to use in medicinal chemistry extensively. Diindolylmethane-based-thiadiazole analogs (1-18) were synthesized and characterized by various spectroscopic techniques 1HNMR, 13C-NMR, EI-MS and evaluated for urease (jack bean urease) inhibitory potential. All compounds showed excellent to moderate inhibitory potential having IC50 value within the range of 0.50 ± 0.01 to 33.20 ± 1.20 µM compared with the standard thiourea (21.60 ± 0.70 µM). Compound 8 (IC50 = 0.50 ± 0.01 µM) was the most potent inhibitor amongst all derivatives. Structure-activity relationships have been established for all compounds. The key binding interactions of most active compounds with enzyme were confirmed through molecular docking studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry Techniques, Synthetic
  • Enzyme Activation
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Hydrogen Bonding
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Models, Biological
  • Molecular Conformation
  • Molecular Structure
  • Protein Binding
  • Structure-Activity Relationship
  • Thiadiazoles / chemistry*
  • Urease / antagonists & inhibitors*
  • Urease / chemistry*

Substances

  • Enzyme Inhibitors
  • Indoles
  • Thiadiazoles
  • Urease
  • 3,3'-diindolylmethane