Synthesis and in vitro evaluation of vanillin derivatives as multi-target therapeutics for the treatment of Alzheimer’s disease
| Autor: | Graeme Kay, Laura Blaikie, Paul Kong Thoo Lin |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Antioxidant DPPH medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science 01 natural sciences Biochemistry Antioxidants Structure-Activity Relationship chemistry.chemical_compound Picrates Alzheimer Disease Drug Discovery medicine Humans Molecular Biology IC50 Cholinesterase Dose-Response Relationship Drug Molecular Structure biology 010405 organic chemistry Vanillin Biphenyl Compounds Organic Chemistry In vitro 0104 chemical sciences 010404 medicinal & biomolecular chemistry Neuroprotective Agents chemistry Benzaldehydes Butyrylcholinesterase Acetylcholinesterase biology.protein Molecular Medicine Cholinesterase Inhibitors Selectivity Lead compound |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 30:127505 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2020.127505 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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