Biochemical Studies on a Novel Potent Acetylcholinesterase Inhibitor with Dualsite Binding for Treatment of Alzheimer’s Disease

Simeonova, Rumyana; Vitcheva, Vessela; Kostadinova, Ivanka; Valkova, Iva; Philipova, Irena; Stavrakov, Georgi; Danchev, Nikolai; Doytchinova, Irini

doi:10.7546/crabs.2021.02.08

Cited by 2 publications

(3 citation statements)

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“…GAL is an AChE inhibitor and has some antioxidant properties acting as a ROS acceptor [ 19 ]. We found similar effects for GAL in our previous studies [ 11 , 20 ], and some other research teams have also found this [ 21 , 22 ].…”

Section: Discussionsupporting

confidence: 91%

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Ex Vivo Antioxidant and Cholinesterase Inhibiting Effects of a Novel Galantamine–Curcumin Hybrid on Scopolamine-Induced Neurotoxicity in Mice

Simeonova

Atanasova

Stavrakov

et al. 2022

IJMS

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Oxidative stress is an essential factor in the development and progression of Alzheimer’s disease (AD). An excessive amount of reactive oxygen species (ROS) induces the peroxidation of lipid membranes, reduces the activity of antioxidant enzymes and causes neurotoxicity. In this study, we investigated the antioxidant and cholinesterase inhibitory potential of a novel galantamine–curcumin hybrid, named 4b, administered orally in two doses (2.5 mg/kg and 5 mg/kg) in scopolamine (SC)-induced neurotoxicity in mice. To evaluate the effects of 4b, we used galantamine (GAL) (3 mg/kg) and curcumin (CCN) (25 mg/kg) as positive controls. Ex vivo experiments on mouse brains showed that the higher dose of 4b (5 mg/kg) increased reduced glutathione (GSH) levels by 46%, catalase (CAT) and superoxide dismutase (SOD) activity by 57%, and glutathione peroxidase (GPx) activity by 108%, compared with the SC-treated group. At the same time, 4b (5 mg/kg) significantly reduced the brain malondialdehyde (MDA) level by 31% and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities by 40% and 30%, respectively, relative to the SC-impaired group. The results showed that 4b acted as an antioxidant agent and brain protector, making it promising for further experimental research in the field of neurodegenerative diseases.

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Section: Discussionsupporting

confidence: 91%

“…Alzheimer’s type dementia was induced by an ip injection of SC 3 mg/kg to male mice for a period of 14 days. To assess the effect of 4b on SC-induced changes on brain biochemical parameters, 40 male mice were divided into ten groups with four mice in each group (n = 4) [ 11 , 20 ].…”

Section: Methodsmentioning

confidence: 99%

Ex Vivo Antioxidant and Cholinesterase Inhibiting Effects of a Novel Galantamine–Curcumin Hybrid on Scopolamine-Induced Neurotoxicity in Mice

Simeonova

Atanasova

Stavrakov

et al. 2022

IJMS

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“…Donepezil (DNPZ) (Pfizer, Manhattan, NY, USA) and scopolamine hydrobromide trihydrate 96% (SC) (Across organics, Shanghai, China), were used in the study. Doses of both pharmaceutical compounds used in this study were chosen based on the information obtained from previous investigations [ 53 , 54 ].…”

Section: Methodsmentioning

confidence: 99%

Tailored Melatonin- and Donepezil-Based Hybrids Targeting Pathognomonic Changes in Alzheimer’s Disease: An In Vitro and In Vivo Investigation

Mihaylova,

Angelova,

Tchekalarova

et al. 2024

IJMS

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A plethora of pathophysiological events have been shown to play a synergistic role in neurodegeneration, revealing multiple potential targets for the pharmacological modulation of Alzheimer’s disease (AD). In continuation to our previous work on new indole- and/or donepezil-based hybrids as neuroprotective agents, the present study reports on the beneficial effects of lead compounds of the series on key pathognomonic features of AD in both cellular and in vivo models. An enzyme-linked immunosorbent assay (ELISA) was used to evaluate the anti-fibrillogenic properties of 15 selected derivatives and identify quantitative changes in the formation of neurotoxic β-amyloid (Aβ42) species in human neuronal cells in response to treatment. Among the most promising compounds were 3a and 3c, which have recently shown excellent antioxidant and anticholinesterase activities, and, therefore, have been subjected to further in vivo investigation in mice. An acute toxicity study was performed after intraperitoneal (i.p.) administration of both compounds, and 1/10 of the LD50 (35 mg/kg) was selected for subacute treatment (14 days) with scopolamine in mice. Donepezil (DNPZ) and/or galantamine (GAL) were used as reference drugs, aiming to establish any pharmacological superiority of the multifaceted approach in battling hallmark features of neurodegeneration. Our promising results give first insights into emerging disease-modifying strategies to combine multiple synergistic activities in a single molecule.

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Biochemical Studies on a Novel Potent Acetylcholinesterase Inhibitor with Dualsite Binding for Treatment of Alzheimer’s Disease

Cited by 2 publications

References 0 publications

Ex Vivo Antioxidant and Cholinesterase Inhibiting Effects of a Novel Galantamine–Curcumin Hybrid on Scopolamine-Induced Neurotoxicity in Mice

Ex Vivo Antioxidant and Cholinesterase Inhibiting Effects of a Novel Galantamine–Curcumin Hybrid on Scopolamine-Induced Neurotoxicity in Mice

Tailored Melatonin- and Donepezil-Based Hybrids Targeting Pathognomonic Changes in Alzheimer’s Disease: An In Vitro and In Vivo Investigation

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