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

Liew, Kok-Fui; Lee, Elaine Hui-Chien; Chan, Kit‐Lam; Lee, Chong Yew

doi:10.1016/j.biopha.2018.11.054

Cited by 11 publications

(1 citation statement)

References 40 publications

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“…However, the aim of the previous report was limited to achieving AChEI and did not include achieving potential polypharmacological candidates. Other related O 6 -aminoalkyl-aurone derivatives appeared in two recent reports that explored very limited methoxylation patterns of aurone's ring-B to provide enough SAR information and, in addition, were investigated only for either AChEI [47] or the inhibition of MAO/β-amyloid aggregation [48]. Furthermore, their MAO inhibition activity was not sufficient.…”

Section: Design Of Focused O 6 -Aminoalkyl Derivatives Of Hispidol An...mentioning

confidence: 99%

Synthesis and Biological Evaluation of O6-Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases

et al. 2023

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Oxidative catabolism of monoamine neurotransmitters by monoamine oxidases (MAOs) produces reactive oxygen species (ROS), which contributes to neuronal cells’ death and also lowers monoamine neurotransmitter levels. In addition, acetylcholinesterase activity and neuroinflammation are involved in neurodegenerative diseases. Herein, we aim to achieve a multifunctional agent that inhibits the oxidative catabolism of monoamine neurotransmitters and, hence, the detrimental production of ROS while enhancing neurotransmitter levels. Such a multifunctional agent might also inhibit acetylcholinesterase and neuroinflammation. To meet this end goal, a series of aminoalkyl derivatives of analogs of the natural product hispidol were designed, synthesized, and evaluated against both monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B). Promising MAO inhibitors were further checked for the inhibition of acetylcholinesterase and neuroinflammation. Among them, compounds 3aa and 3bc were identified as potential multifunctional molecules eliciting submicromolar selective MAO-B inhibition, low-micromolar AChE inhibition, and the inhibition of microglial PGE2 production. An evaluation of their effects on memory and cognitive impairments using a passive avoidance test confirmed the in vivo activity of compound 3bc, which showed comparable activity to donepezil. In silico molecular docking provided insights into the MAO and acetylcholinesterase inhibitory activities of compounds 3aa and 3bc. These findings suggest compound 3bc as a potential lead for the further development of agents against neurodegenerative diseases.

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Section: Design Of Focused O 6 -Aminoalkyl Derivatives Of Hispidol An...mentioning

confidence: 99%

Synthesis and Biological Evaluation of O6-Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases

et al. 2023

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Design, synthesis, and biological activity studies of a new class of sulfonated aurones: First synthesis of acidoaurone isolated from Phyllanthus acidus

Venkateswarlu

Murty

Satyanarayana

et al. 2021

Journal of Heterocyclic Chem

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A novel series of aurones were designed by introducing sulfonic acid group on ring-A and ring-B of known natural aurones such as hispidol, sulfuretin, maritimetin, and aureusidin. These sulfonated aurones were synthesized by a unique approach. Sulfonation on ring-A or ring-B converts water-insoluble aurones into highly water-soluble aurones. The sulfonated aurones were tested for their antioxidant, antiinflammatory, and AChE inhibition activities along with their natural aurones. Ring-A sulfonated aurones displayed higher antioxidant activity, 5-LOX, and AChE inhibition in comparison with their corresponding natural aurones. Ring-B sulfonated aurones exhibited potent 5-LOX inhibitory activity and significant antioxidant activity. Acidoaurone, a first sulfonated aurone isolated from Phyllanthus acidus was synthesized for the first time and was well characterized using NMR, LC-MS, and further confirmed by HMBC.

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Chalcone and its analogs: Therapeutic and diagnostic applications in Alzheimer’s disease

Thapa

Upadhyay

Suo

et al. 2021

Bioorganic Chemistry

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

Cited by 11 publications

References 40 publications

Synthesis and Biological Evaluation of O6-Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases

Synthesis and Biological Evaluation of O6-Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases

Design, synthesis, and biological activity studies of a new class of sulfonated aurones: First synthesis of acidoaurone isolated from Phyllanthus acidus

Chalcone and its analogs: Therapeutic and diagnostic applications in Alzheimer’s disease

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