Multi-targeting aurones with monoamine oxidase and amyloid-beta inhibitory activities: structure-activity relationship and translating multi-potency to neuroprotection

Liew, K.-F., Lee, E. H.-C., Chan, K. L. and Lee, C. Y. (2019) Multi-targeting aurones with monoamine oxidase and amyloid-beta inhibitory activities: structure-activity relationship and translating multi-potency to neuroprotection. Biomedicine & Pharmacotherapy, 110. pp. 118-128. ISSN 0753-3322 doi: 10.1016/j.biopha.2018.11.054

Abstract/Summary

Previously, a series of aurones bearing amine and carbamate functionalities was synthesized and evaluated for their cholinesterase inhibitory activity and drug-like attributes. In the present study, these aurones were evaluated for their multi-targeting properties in two Alzheimer’s disease (AD)-related activities namely, monoamine oxidase (MAO) and amyloid-beta (Aβ) inhibition. Evaluation of the aurones for MAO inhibitory activity disclosed several potent selective inhibitors of MAO-B, particularly those with 6-methoxyl group attached at ring A. Of the different amine moieties attached as side chains, pyrrolidine-bearing aurones were prominent as represented by 2-2, the most potent inhibitor. Evaluation on the Aβ aggregation inhibition identified 4-3 as the best inhibitor with a percentage inhibition comparable to that of a known Aβ inhibitor curcumin. Examination on the neuroprotective ability of the more drug-like aurone 4-3 in two Caenorhabditis elegans neurodegeneration models showed 4-3 to protect the nematodes against both Aβ- and 6-hydroxydopamine-induced toxicities. These new activities further support 4-3 as a promising lead to develop the aurones as potential multipotent agents for neurodegenerative diseases.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/80549
Identification Number/DOI	10.1016/j.biopha.2018.11.054
Refereed	Yes
Divisions	University of Reading Malaysia
Publisher	Elsevier
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