Bioorg Med Chem Lett
School of Science, Penn State Erie, The Behrend College, Erie, PA 16563, USA. Electronic address:
Published: December 2022
Polymethylene-linked isatin dimers 1a-g and 3-indolyl-3-hydroxy-2-oxindole dimers 2a-g were synthesized and are reported here as selective butyrylcholinesterase (BChE) inhibitors. The best compound from each series, 1f and 2d, showed IC values of 3.20 µM and 4.49 µM, respectively. Both compounds showed > 11-fold selectivity towards BChE, and mixed-type inhibition by Lineweaver-Burk analysis. These two inhibitors shared π-π stacking interactions with Trp82 and H-bonding to Gly116 and Ser198, the catalytic Ser of the enzyme triad, within the BChE active site as predicted by molecular docking. Compound 1d was also shown to be good inhibitor with an IC of 7.56 µM, and it shares the same pentamethylene linker as 2d. Inhibitors 1d, 1f, and 2d were predicted to have moderate, low, and moderate blood-brain barrier (BBB) permeability, respectively, making them, overall, promising lead compounds for further exploration of selective BChE inhibitors.
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http://dx.doi.org/10.1016/j.bmcl.2022.129037 | DOI Listing |
Chem Res Toxicol
January 2025
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Highway NE, Atlanta, Georgia 30341, United States.
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Department of Pharmaceutical Sciences, Guru Nanak Dev University Amritsar Punjab 143005 India
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November 2024
Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland.
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Genes (Basel)
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