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Structure-guided modification of a lead cholinesterase-targeting oxime to improve peripheral site binding Cover

Structure-guided modification of a lead cholinesterase-targeting oxime to improve peripheral site binding

Archives of Industrial Hygiene and Toxicology
Volume 77 (2026): Issue 1 (March 2026)
By: Nikola Maraković,  Nicolas Probst,  Tena Čadež and  Antonio Zandona  
Open Access
|Mar 2026
Figures & tables

Figures & Tables

Figure 1

A) N-substituted 2-hydroxyiminoacetamides 1 and 2; B) crystallographic structure of oxime (R)-1 bound to human BChE (PDB: 6T9P). Non-covalent interactions are shown: hydrogen bonds (green dashed lines) and π interactions (magenta dashed lines). 1 – 2-hydroxyimino-N-(3-(4-((2-methyl-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)-1-phenylpropyl)acetamide; 2 – N-(3-(4-((6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-1H-1,2,3-triazol-1-yl)-1-phenylpropyl)-2-(hydroxyimino)acetamide

Figure 2

Synthesis of the test compound N-(3-(4-((6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-1H-1,2,3-triazol-1-yl)-1-phenylpropyl)-2-(hydroxyimino)acetamide. 2 – N-(3-(4-((6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-1H-1,2,3-triazol-1-yl)-1-phenylpropyl)-2-(hydroxyimino) acetamide; 3 – N-(3-azido-1-phenylpropyl)-2-hydroxyiminoacetamide; 4 – 6,7-dimethoxy-2-(prop-2-yn-1-yl)-1,2,3,4-tetrahydroisoquinoline

Figure 3

Model complexes of the test compound N-(3-(4-((6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-1H-1,2,3-triazol-1-yl)-1-phenylpropyl)-2-(hydroxyimino)acetamide and human BChE (A) or human AChE (B–D). Dashed lines represent different types of non-bonding interactions (magenta – π-alkyl, π-π interaction; green – conventional hydrogen bond; light green – carbon hydrogen bond; blue – water hydrogen bond). Red spheres show only those water molecules (hydrogens hidden) predicted to interact with ligands

Reversible inhibition of human red blood cell acetylcholinesterase (AChE) and human plasma butyrylcholinesterase (BChE) by the test compound N-(3-(4-((6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-1H-1,2,3-triazol-1-yl)-1-phenylpropyl)-2-(hydroxyimino)acetamide

EnzymeAcetylthiocholine (mmol/L)Concentration range (µmol/L)KI (µmol/L)
AChE0.1–1.025–7549±4
BChE0.1–1.05–3018±1
DOI: https://doi.org/10.2478/aiht-2026-77-4078 | Journal eISSN: 1848-6312 | Journal ISSN: 0004-1254
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Language: English, Croatian, Slovenian
Page range: 1 - 8
Submitted on: Nov 1, 2025
Accepted on: Feb 1, 2026
Published on: Mar 30, 2026
Published by: Institute for Medical Research and Occupational Health
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
2-hydroxyiminoacetamides,
acetylcholinesterase,
butyrylcholinesterase,
cycloaddition,
tetrahydroisoquinoline
Related subjects:
Medicine,
Basic medical science,
Basic medical science, other

© 2026 Nikola Maraković, Nicolas Probst, Tena Čadež, Antonio Zandona, published by Institute for Medical Research and Occupational Health
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 77 (2026): Issue 1 (March 2026)
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