Coumarin-azasugar-benzyl conjugates as non-neurotoxic dual inhibitors of butyrylcholinesterase and cancer cell growth.

Autor:	Vaaland Holmgard IC; Department of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway. emil.lindback@uis.no., González-Bakker A; BioLab, Instituto Universitario de Bio-Orgánica 'Antonio González' (IUBO-AG), Universidad de La Laguna, c/Astrofísico Francisco Sánchez 2, La Laguna, E-38206, Spain., Poeta E; Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy., Puerta A; BioLab, Instituto Universitario de Bio-Orgánica 'Antonio González' (IUBO-AG), Universidad de La Laguna, c/Astrofísico Francisco Sánchez 2, La Laguna, E-38206, Spain., Fernandes MX; Department of Engineering and Chemical Sciences, Karlstad University, Karlstad, Sweden., Monti B; Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy., Fernández-Bolaños JG; Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Seville, Spain., Padrón JM; BioLab, Instituto Universitario de Bio-Orgánica 'Antonio González' (IUBO-AG), Universidad de La Laguna, c/Astrofísico Francisco Sánchez 2, La Laguna, E-38206, Spain., López Ó; Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Seville, Spain., Lindbäck E; Department of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway. emil.lindback@uis.no.
Jazyk:	angličtina
Zdroj:	Organic & biomolecular chemistry [Org Biomol Chem] 2024 May 01; Vol. 22 (17), pp. 3425-3438. Date of Electronic Publication: 2024 May 01.
DOI:	10.1039/d4ob00312h
Abstrakt:	We have applied the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to prepare a library of ten coumarin-azasugar-benzyl conjugates and two phthalimide-azasugar-benzyl conjugates with potential anti-Alzheimer and anti-cancer properties. The compounds were evaluated as cholinesterase inhibitors, demonstrating a general preference, of up to 676-fold, for the inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE). Nine of the compounds behaved as stronger BuChE inhibitors than galantamine, one of the few drugs in clinical use against Alzheimer's disease. The most potent BuChE inhibitor (IC 50 = 74 nM) was found to exhibit dual activities, as it also showed high activity (GI 50 = 5.6 ± 1.1 μM) for inhibiting the growth of WiDr (colon cancer cells). In vitro studies on this dual-activity compound on Cerebellar Granule Neurons (CGNs) demonstrated that it displays no neurotoxicity.
Databáze:	MEDLINE
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