Design, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer’s disease agents

Simple item page
dc.contributor.authorMzezewa, Sheunopa C.
dc.contributor.authorOmoruyi, Sylvester I.
dc.contributor.authorZondagh, Luke S.
dc.date.accessioned2022-01-18T08:13:59Z
dc.date.available2022-01-18T08:13:59Z
dc.date.issued2021
dc.description.abstractMultitarget 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.en_US
dc.identifier.citationMzezewa, 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/10.1080/14756366.2021.1913137en_US
dc.identifier.issn1475-6374
dc.identifier.urihttps://doi.org/10.1080/14756366.2021.1913137
dc.identifier.urihttp://hdl.handle.net/10566/7113
dc.language.isoenen_US
dc.publisherTaylor & Francis Open Accessen_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectNeuroprotectionen_US
dc.subjectCoumarin derivativesen_US
dc.subjectMonoamine oxidaseen_US
dc.subjectPharmacy educationen_US
dc.subjectMemory lossen_US
dc.titleDesign, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer’s disease agentsen_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Design synthesis and evaluation of 3 7 substituted coumarin derivatives as multifunctional Alzheimer s disease agents (1).pdf
Size:
3.36 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Research Articles (School of Pharmacy)