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Synthesis and in vitro evaluation of vanillin derivatives as multi-target therapeutics for the treatment of Alzheimer's disease.

Authors
  • Blaikie, Laura1
  • Kay, Graeme1
  • Kong Thoo Lin, Paul2
  • 1 School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen, Scotland, United Kingdom. , (United Kingdom)
  • 2 School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen, Scotland, United Kingdom. Electronic address: [email protected] , (United Kingdom)
Type
Published Article
Journal
Bioorganic & medicinal chemistry letters
Publication Date
Aug 19, 2020
Volume
30
Issue
21
Pages
127505–127505
Identifiers
DOI: 10.1016/j.bmcl.2020.127505
PMID: 32822761
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

A number of novel naphthalimido and phthalimido vanillin derivatives were synthesised, and evaluated as antioxidants and cholinesterase inhibitors in vitro. Antioxidant activity was assessed using DPPH, FRAP, and ORAC assays. All compounds demonstrated enhanced activity compared to the parent compound, vanillin. They also exhibited BuChE selectivity in Ellman's assay. A lead compound, 2a (2-(3-(bis(4-hydroxy-3-methoxybenzyl)amino)propyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione), was identified and displayed strong antioxidant activity (IC50 of 16.67 µM in the DPPH assay, a 25-fold increase in activity compared to vanillin in the FRAP assay, and 9.43 TE in the ORAC assay). Furthermore, 2a exhibited potent BuChE selectivity, with an IC50 of 0.27 µM which was around 53-fold greater than the corresponding AChE inhibitory activity. Molecular modelling studies showed that molecules with bulkier groups, as in 2a, exhibited better BuChE selectivity. This work provides a promising basis for the development of multi-target hybrid compounds based on vanillin as potential AD therapeutics. Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.

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