Bisindolylmethane thiosemicarbazides as potential inhibitors of urease: Synthesis and molecular modeling studies

Bioorg Med Chem. 2018 Jan 1;26(1):152-160. doi: 10.1016/j.bmc.2017.11.028. Epub 2017 Nov 21.

Abstract

Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC50 values ranging between 0.14 ± 0.01 to 18.50 ± 0.90 μM when compared with the standard inhibitor thiourea having IC50 value 21.25 ± 0.90 μM. Among the series, analog 9 (0.14 ± 0.01 μM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies.

Keywords: Bisindole; Molecular docking; SAR; Synthèsis; Urease inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Canavalia / enzymology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Semicarbazides / chemistry
  • Semicarbazides / pharmacology*
  • Structure-Activity Relationship
  • Urease / antagonists & inhibitors*
  • Urease / metabolism

Substances

  • Enzyme Inhibitors
  • Indoles
  • Semicarbazides
  • thiosemicarbazide
  • Urease
  • 3,3'-diindolylmethane