(S)- N-Benzyl-1-phenyl-3,4-dihydroisoqunoline-2(1 H)-carboxamide Derivatives, Multi-Target Inhibitors of Monoamine Oxidase and Cholinesterase: Design, Synthesis, and Biological Activity

Molecules. 2023 Feb 9;28(4):1654. doi: 10.3390/molecules28041654.

Abstract

A series of (S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives was synthesized and evaluated for inhibitory activity against monoamine oxidase (MAO)-A and-B, acetylcholine esterase (AChE), and butyrylcholine esterase (BChE). Four compounds (2i, 2p, 2t, and 2v) showed good inhibitory activity against both MAO-A and MAO-B, and two compounds (2d and 2j) showed selective inhibitory activity against MAO-A, with IC50 values of 1.38 and 2.48 µM, respectively. None of the compounds showed inhibitory activity against AChE; however, 12 compounds showed inhibitory activity against BChE. None of the active compounds showed cytotoxicity against L929cells. Molecular docking revealed several important interactions between the active analogs and amino acid residues of the protein receptors. This research paves the way for further study aimed at designing MAO and ChE inhibitors for the treatment of depression and neurodegenerative disorders.

Keywords: 3,4-dihydroisoquinoline; carboxamide derivatives; cholinesterase; cytotoxicity; molecular docking; monoamine oxidase.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterases* / metabolism
  • Molecular Docking Simulation
  • Monoamine Oxidase Inhibitors / pharmacology
  • Monoamine Oxidase* / metabolism
  • Structure-Activity Relationship

Substances

  • Monoamine Oxidase
  • Cholinesterases
  • Monoamine Oxidase Inhibitors
  • Cholinesterase Inhibitors
  • Acetylcholinesterase

Grants and funding

This research received no external funding.