Synthesis and properties of the kojic acid dimer and its potential for the treatment of Alzheimer's disease

Liu, Xueyan; Yu, Chuanyu; Su, Baogen; Zha, Daijun

doi:10.1039/d2md00383j

Cited by 3 publications

(2 citation statements)

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“…Yellow solid; yield: 71% (10.96 g); R f : 0.21 (petroleum ether/ethyl acetate, 1:2, v/v). 1 H NMR , 13 C NMR and HRMS have been reported in our previous work 40 .…”

Section: Methodsmentioning

confidence: 85%

Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer’s disease

Yu,

Liu,

et al. 2024

Journal of Enzyme Inhibition and Medicinal Chemistry

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Butyrylcholinesterase (BuChE) and neuroinflammation have recently emerged as promising therapeutic directions for Alzheimer’s disease (AD). Herein, we synthesised 19 novel pyranone-carbamate derivatives and evaluated their activities against cholinesterases and neuroinflammation. The optimal compound 7p exhibited balanced BuChE inhibitory activity (eqBuChE IC 50 = 4.68 nM; huBuChE IC 50 = 9.12 nM) and anti-neuroinflammatory activity (NO inhibition = 28.82% at 10 μM, comparable to hydrocortisone). Enzyme kinetic and docking studies confirmed compound 7p was a mix-type BuChE inhibitor. Additionally, compound 7p displayed favourable drug-likeness properties in silico prediction, and exhibited high BBB permeability in the PAMPA-BBB assay. Compound 7p had good safety in vivo as verified by an acute toxicity assay (LD 50 > 1000 mg/kg). Most importantly, compound 7p effectively mitigated cognitive and memory impairments in the scopolamine-induced mouse model, showing comparable effects to Rivastigmine. Therefore, we envisioned that compound 7p could serve as a promising lead compound for treating AD.

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“…Yellow solid; yield: 71% (10.96 g); R f : 0.21 (petroleum ether/ethyl acetate, 1:2, v/v). 1 H NMR , 13 C NMR and HRMS have been reported in our previous work 40 .…”

Section: Methodsmentioning

confidence: 85%

Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer’s disease

Yu,

Liu,

et al. 2024

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…, using 5-amino isophthalic acid, with its amino functionality and aromatic character, is anticipated to introduce desirable electronic properties to the triazole backbone. Concurrently, the inclusion of kojic acid, renowned for its chelating capabilities and excellent coordination properties, 24,25 can add an element of selectivity and sensitivity to the synthesized chemosensor, particularly in the context of metal ion recognition. Molecular docking, a powerful computational technique, was used to investigate the interaction between the probe and selected microbial targets.…”

Section: Introductionmentioning

confidence: 99%

5-Aminoisophthalate-based kojic acid-appended bis-1,2,3-triazole: a fluorescent chemosensor for Cu²⁺ sensing and in silico study

Kumar,

Lal,

Singh

et al. 2024

RSC Adv.

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Kojic acid reverses LPS-induced neuroinflammation and cognitive impairment by regulating the TLR4/NF-κB signaling pathway

Ali,

Choe,

Park

et al. 2024

Front. Pharmacol.

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Intense neuroinflammation contributes to neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Lipopolysaccharides (LPSs) are an integral part of the cell wall of Gram-negative bacteria that act as pathogen-associated molecular patterns (PAMPs) and potentially activate the central nervous system’s (CNS) immune system. Microglial cells are the local macrophages of the CNS and have the potential to induce and control neuroinflammation. This study aims to evaluate the anti-inflammatory and antioxidant effect of kojic acid against the toxic effects of LPSs, such as neuroinflammation-induced neurodegeneration and cognitive decline. The C57BL/6N mice were subjected to LPS injection for 2 weeks on alternate days (each mouse received 0.25 mg/kg/i.p. for a total of seven doses), and kojic acid was administered orally for 3 weeks consecutively (50 mg/kg/mouse, p. o). Bacterial endotoxins, or LPSs, are directly attached to TLR4 surface receptors of microglia and astrocytes and alter the cellular metabolism of immune cells. Intraperitoneal injection of LPS triggers the toll-like receptor 4 (TLR4), phospho-nuclear factor kappa B (p-NFκB), and phospho-c-Jun n-terminal kinase (p-JNK) protein expressions in the LPS-treated group, but these expression levels were significantly downregulated in the LPS + KA-treated mice brains. Prolong neuroinflammation leads to the generation of reactive oxygen species (ROS) followed by a decrease in nuclear factor erythroid-2-related factor 2 (Nrf2) and the enzyme hemeoxygenase 1 (HO-1) expression in LPS-subjected mouse brains. Interestingly, the levels of both Nrf-2 and HO-1 increased in the LPS + KA-treated mice group. In addition, kojic acid inhibited LPS-induced TNF-α and IL-1β production in mouse brains. These results indicated that kojic acid may suppress LPS-induced neuroinflammation and oxidative stress in male wild-type mice brains (in both the cortex and the hippocampus) by regulating the TLR4/NF-κB signaling pathway.

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Synthesis and properties of the kojic acid dimer and its potential for the treatment of Alzheimer's disease

Abstract: Kojic acid dimer (KAD) is a metabolite derived from developing cottonseed when contaminated with aflatoxin. KAD has been shown to exhibit bright greenish-yellow fluorescence, but little else is known about...

Cited by 3 publications

References 47 publications

Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer’s disease

Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer’s disease

5-Aminoisophthalate-based kojic acid-appended bis-1,2,3-triazole: a fluorescent chemosensor for Cu²⁺ sensing and in silico study

Kojic acid reverses LPS-induced neuroinflammation and cognitive impairment by regulating the TLR4/NF-κB signaling pathway

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Synthesis and properties of the kojic acid dimer and its potential for the treatment of Alzheimer's disease

Abstract: Kojic acid dimer (KAD) is a metabolite derived from developing cottonseed when contaminated with aflatoxin. KAD has been shown to exhibit bright greenish-yellow fluorescence, but little else is known about...

Cited by 3 publications

References 47 publications

Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer’s disease

Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer’s disease

5-Aminoisophthalate-based kojic acid-appended bis-1,2,3-triazole: a fluorescent chemosensor for Cu2+ sensing and in silico study

Kojic acid reverses LPS-induced neuroinflammation and cognitive impairment by regulating the TLR4/NF-κB signaling pathway

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5-Aminoisophthalate-based kojic acid-appended bis-1,2,3-triazole: a fluorescent chemosensor for Cu²⁺ sensing and in silico study