Dispiropyrrolidinyl-piperidone embedded indeno[1,2-b]quinoxaline heterocyclic hybrids: Synthesis, cholinesterase inhibitory activity and their molecular docking simulation

Bioorg Med Chem. 2019 Jun 15;27(12):2621-2628. doi: 10.1016/j.bmc.2019.03.058. Epub 2019 Mar 30.

Abstract

A small library of new class of dispiropyrrolidinyl-piperidone tethered indono[1,2-b]quinoxaline heterocyclic hybrids 7a-j were synthesized employing multicomponent 1,3-dipolar cycloaddition strategy in [bmim]Br. The azomethine ylide employed is first of its kind and generated in situ from indenoquinoxalinone and l-tryptophan, a combination that has not been employed previously for the in situ generation of azomethine ylides. The synthesized heterocyclic hybrids 7a-j were evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, therein compounds 7h and 7j displayed more potent AChE and BChE enzyme inhibition than the standard drug with IC50 values of 3.22, 2.01, 12.40 and 10.45 mM, respectively. Molecular docking studies have also been investigated for most active compounds that disclosed interesting binding templates to the active site channel of cholinesterase enzyme.

Keywords: AChE and BChE activity; Molecular docking simulation; Multicomponent 1,3-dipolar cycloaddition; Spiropyrrolidines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism*
  • Binding Sites
  • Butyrylcholinesterase / chemistry
  • Butyrylcholinesterase / metabolism*
  • Catalytic Domain
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacokinetics
  • Half-Life
  • Humans
  • Inhibitory Concentration 50
  • Molecular Docking Simulation*
  • Piperidones / chemistry*
  • Quinoxalines / chemistry*
  • Solubility

Substances

  • Cholinesterase Inhibitors
  • Piperidones
  • Quinoxalines
  • Acetylcholinesterase
  • Butyrylcholinesterase