Synthesis of novel triazoles and a tetrazole of escitalopram as cholinesterase inhibitors

Bioorg Med Chem. 2015 Sep 1;23(17):6014-24. doi: 10.1016/j.bmc.2015.06.051. Epub 2015 Jun 26.

Abstract

A novel serie of escitalopram triazoles (60-88) and a tetrazole (89) have been synthesized and subjected to a study to establish the inhibitory potential of these compounds toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Some selectivity in inhibition has been observed. The 4-chlorophenyl- (75, IC50, 6.71 ± 0.25 μM) and 2-methylphenyl- (70, IC50, 9.52 ± 0.23 μM) escitalopram triazole derivatives depicted high AChE inhibition, while 2-fluorophenyl- (76, IC50 = 4.52 ± 0.17 μM) and 4-fluorophenyl- (78, IC50 = 5.31 ± 0.43 μM) have found to be excellent BChE inhibitors. It has also been observed that ortho, meta and para substituted electron donating groups increase the inhibition, while electron withdrawing groups reduce the inhibition. Docking analyses of inhibitors with AChE have depicted the binding energies for 70 and 75 as ΔG(bind) -6.42 and -6.93 kcal/mol, respectively, while ligands 76 and 78 have shown the binding affinity ΔG(bind) -9.04 and -8.51 kcal/mol, respectively, for BChE.

Keywords: Acetylcholinesterase; Butyrylcholinesterase; Cholinesterase; Escitalopram; Triazoles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholinesterase Inhibitors / chemistry
  • Citalopram / chemical synthesis*
  • Citalopram / chemistry*
  • Molecular Structure
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry*

Substances

  • Cholinesterase Inhibitors
  • Triazoles
  • Citalopram