Anticholinesterase activity of β-carboline-1,3,5-triazine hybrids

Paula Baréa; Valéria Aquilino Barbosa; Diego Alberto dos Santos Yamazaki; Carla Maria Beraldi Gomes; Claudio R. Novello; Willian Ferreira da Costa; Gisele de Freitas Gauze; Maria Helena Sarragiotto

doi:10.1590/s2175-97902022e19958

Authors

Paula Baréa State University of Maringá (UEM), Chemistry Department, PR, Brazil https://orcid.org/0000-0002-9809-6666
Valéria Aquilino Barbosa State University of Maringá (UEM), Chemistry Department, PR, Brazil
Diego Alberto dos Santos Yamazaki State University of Maringá (UEM), Chemistry Department, PR, Brazil
Carla Maria Beraldi Gomes State University of Maringá (UEM), Chemistry Department, PR, Brazil
Claudio R. Novello Federal Technological University of Paraná, Department of Chemistry and Biology, Francisco Beltrão-PR, Brazil
Willian Ferreira da Costa State University of Maringá (UEM), Chemistry Department, PR, Brazil
Gisele de Freitas Gauze State University of Maringá (UEM), Chemistry Department, PR, Brazil
Maria Helena Sarragiotto State University of Maringá (UEM), Chemistry Department, PR, Brazil https://orcid.org/0000-0003-3861-502X

DOI:

https://doi.org/10.1590/s2175-97902022e19958

Keywords:

β-carboline, 1,3,5-triazine, Acetylcholinesterase, Butyrylcholinesterase

Abstract

The β-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC₅₀ values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-β-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine.

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Anticholinesterase activity of β-carboline-1,3,5-triazine hybrids

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