Design, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer’s disease agents
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Taylor & Francis Open Access
Abstract
Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alzheimer’s disease
(AD). Coumarin derivatives serve as a good starting point for designing MTDLs due to their inherent inhibition of monoamine oxidase (MAO) and cholinesterase enzymes, which are complicit in AD’s complex
pathophysiology. A preliminary series of 3,7-substituted coumarin derivatives were synthesised and evaluated for enzyme inhibitory activity, cytotoxicity as well as neuroprotective ability. The results indicated
that the compounds are weak cholinesterase inhibitors with five compounds demonstrating relatively
potent inhibition and selectivity towards MAO-B with IC50 values between 0.014 and 0.498 hx00B5;mM.
Significant neuroprotective effects towards MPPþ-compromised SH-SY5Y neuroblastoma cells were also
observed, with no inherent cytotoxicity at 10 mM for all compounds. The overall results demonstrated that
substitution of the phenylethyloxy moiety at the 7-position imparted superior general activity to the derivatives, with the propargylamine substitution at the 3-position, in particular, displaying the best MAO-B
selectivity and neuroprotection.
Description
Keywords
Alzheimer’s disease, Neuroprotection, Coumarin derivatives, Monoamine oxidase, Pharmacy education, Memory loss
Citation
Mzezewa, S. C. et al. (2021). Design, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer’s disease agents. Journal of Enzyme Inhibition and Medicinal Chemistry ,36(1),1606–1620. https://doi.org/10.1080/14756366.2021.1913137