Novel tribenzylaminobenzolsulphonylimine based on their pyrazine and pyridazines: Synthesis, characterization, antidiabetic, anticancer, anticholinergic, and molecular docking studies

Bioorg Chem. 2019 Dec:93:103313. doi: 10.1016/j.bioorg.2019.103313. Epub 2019 Sep 24.

Abstract

A new method of obtaining multifunctional pyrazoles by the reaction of 1,3-dipolar addition of tribenzylsulfonyliminochloride to polarophiles has been developed. This imine is obtained by reacting tribenzylamine with N-chlorobenzene sulfamide (chloramine-B). Regardless of the structure and composition of polarophiles, the cyclization reaction takes place in the presence of alkali in 6-8 h of boiling, which proves the activation of the methylene groups of tribenzylamine using the electron-withdrawing sulfonamide group. These novel derivatives were effective inhibitors of the α-glycosidase, butyrylcholinesterase (BChE), and acetylcholinesterase enzymes (AChE) with Ki values in the range of 0.45 ± 0.08-1.24 ± 0.27 µM for α-glycosidase, 6.04 ± 0.95-11.61 ± 2.84 µM for BChE, and 2.04 ± 0.24-4.23 ± 1.02 µM for AChE, respectively. The biological activities of the studied molecules against enzyme molecules were investigated by molecular docking calculations. The enzymes studied were AChE for ID 4M0E, BChE for ID 5NN0 BChE, and α-Glycosidase for ID 1XSI (α-Gly) respectively.

Keywords: Anticancer; Cholinesterase; Enzyme inhibition; Molecular docking; Pyrazole; Sulfamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Butyrylcholinesterase / chemistry
  • Butyrylcholinesterase / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cholinergic Antagonists / chemical synthesis*
  • Cholinergic Antagonists / metabolism
  • Cholinergic Antagonists / pharmacology
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacology
  • Humans
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacology
  • Imines / chemistry*
  • Imines / metabolism
  • Imines / pharmacology
  • Kinetics
  • Molecular Docking Simulation*
  • Protein Structure, Tertiary
  • Pyrazines / chemistry
  • Pyridazines / chemistry
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Cholinergic Antagonists
  • Cholinesterase Inhibitors
  • Hypoglycemic Agents
  • Imines
  • Pyrazines
  • Pyridazines
  • Acetylcholinesterase
  • Butyrylcholinesterase