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

Document Type

Article

Publication Date

3-1-2020

Abstract

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. © 2019 Elsevier B.V.

Keywords

Tetrahydro-β-carboline, Single crystal, Acetylcholinesterase, Molecular docking, Cytotoxicity, ADMET

Divisions

CHEMISTRY

Funders

Research University (RUT) Grant Scheme (1001/CDADAH/855005) and Research University (RUI) Grant Scheme (1001/CDADAH/8011075), Universiti Sains Malaysia, Malaysia,Ministry of Higher Education of Malaysia under the HICoE Programme (311/CDADAH/4401009)

Publication Title

Journal of Molecular Structure

Volume

1200

Publisher

Elsevier

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