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Updated: Sep 11, 2025

Identification of Small Molecule-binding Proteins in a Native Cellular Environment by Live-cell Photoaffinity Labeling
Published on: September 20, 2016
Photochemistry-driven design of small molecule cholinesterase ligands
Irena Škorić1, Maja Sviben1, Milena Mlakić1
1Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Trg Marka Marulića 19, HR-10000, Zagreb, Croatia.
None:
The development of small-molecule ligands targeting cholinesterases remains a central focus in neuropharmacology, particularly for the treatment of neurodegenerative disorders and organophosphate poisoning. This review highlights the rational design, synthesis, and biological profiling of diverse classes of heterocyclic compounds - including oxazoles, heterostilbenes, triazoles, and bicyclo[3.2.1]octane/octadiene derivatives - as reversible inhibitors and reactivators of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Novel amino-oxazolostilbenes and their photoproducts exhibited selective BChE inhibition, while naphtoxazole and triazole-containing scaffolds demonstrated promising dual-target or BChE-selective profiles. Several uncharged oximes, such as thienostilbene and heterostilbene oximes, showed potential for reactivating cyclosarin-inhibited BChE, supporting their further development as CNS-permeable antidotes. Additionally, resveratrol-based triazoles and carbamates revealed enhanced BChE inhibition, antioxidant activity, and favorable selectivity. Collectively, these findings underscore the therapeutic potential of structurally diverse cholinesterase ligands and provide a framework for the discovery of multifunctional agents for Alzheimer's disease and chemical threat countermeasures.
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