Synthesis, characterization and crystal structure of new tetrahydro-β-carboline as acetylcholinesterase inhibitor

In this study, a new tetrahydro-β-carboline derivative, 2-benzoyl-6-methoxy-9-methyl-1-phenyl-1,2,3,4-tetrahydro-β-carboline has been synthesized through a three-steps reaction in good yield (76%). The structure of this compound was characterized by different spectroscopic methods including NMR (1D and 2D), UV, IR and MS. Molecular structure of the synthesized compound was also confirmed by single crystal X-ray diffraction technique. Further, evaluation of in vitro acetylcholinesterase (AChE) inhibitory activity showcased the potential of this compound as AChE inhibitor with an IC50 value of 26.52 ± 0.79 μM. In addition, this compound showed minimal toxicological profile at cellular level. Docking simulation illustrated a highly selective binding at peripheral side of AChE via hydrophobic interactions. In silico prediction of blood-brain barrier (BBB) permeation and ADMET properties of the compound was also reported. [Display omitted] •Synthesis and spectroscopic analysis (IR, UV, 1D and 2D NMR) of a new tetrahydro-β-carboline derivative (3).•X-ray crystallographic analysis of compound 3.•The AChE inhibition and cytotoxic studies of compound 3 and its intermediates.•Molecular docking of compound 3 on active site of AChE.•In silico prediction of BBB permeation and ADMET properties of title compound.