Role of Acetylcholinesterase Inhibitors and Alzheimer Disease

Saify, Zafar Saied

doi:10.1016/b978-0-12-803959-5.50007-6

Cited by 9 publications

(4 citation statements)

References 153 publications

(76 reference statements)

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“…The cholinergic system in neuroinflammatory disorders is unbalanced [ 38 ]. AChE inhibitors enhance cognition [ 39 ] and are the most effective therapy for treating AD patients [ 40 ]. LPS increased the activity of AChE in mice brains, which is consistent with a previous study by Tyagi et al [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antiviral Effect and Potential Neuroprotection of Salvadora persica L. Stem Bark Extract against Lipopolysaccharides-Induced Neuroinflammation in Mice: LC-ESI-MS/MS Analysis of the Methanol Extract

et al. 2023

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Neuroinflammation is a serious immunomodulatory complex disorder that causes neurological and somatic ailments. The treatment of brain inflammation with new drugs derived from natural sources is a significant therapeutic goal. Utilizing LC-ESI-MS/MS analysis, the active constituents of Salvadora persica extract (SPE) were identified tentatively as exerting antioxidant and anti-inflammatory effects in natural medicine. Herein, we determined the antiviral potential of SPE against herpes simplex virus type 2 (HSV-2) using the plaque assay. HSV-2 is a neurotropic virus that can cause neurological diseases. SPE exhibited promising antiviral potential with a half-maximal cytotoxic concentration (CC50) of 185.960 ± 0.1 µg/mL and a half-maximal inhibitory concentration (IC50) of 8.946 ± 0.02 µg/mL. The in vivo study of the SPE impact against lipopolysaccharide (LPS)-induced neuroinflammation was performed using 42 mice divided into seven groups. All groups were administered LPS (0.25 mg/kg) intraperitoneally, except for the normal and SPE groups 1 and 2. Groups 5, 6, and 7 received 100, 200, and 300 mg/kg SPE. It was revealed that SPE inhibited acetylcholinesterase in the brain. It increased superoxide dismutase and catalase while decreasing malondialdehyde, which explains its antioxidative stress activity. SPE downregulated the gene expression of the inducible nitric oxide synthase, as well as the apoptotic markers (caspase-3 and c-Jun). In addition, it decreased the expression of the proinflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha). Mice administered SPE (300 mg/kg) with LPS exhibited normal neurons in the cerebral cortices, hippocampus pyramidal layer, and cerebellum, as determined by the histopathological analysis. Therefore, using S. persica to prevent and treat neurodegeneration could be a promising new therapeutic strategy to be explored.

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Section: Discussionmentioning

confidence: 99%

In Vitro Antiviral Effect and Potential Neuroprotection of Salvadora persica L. Stem Bark Extract against Lipopolysaccharides-Induced Neuroinflammation in Mice: LC-ESI-MS/MS Analysis of the Methanol Extract

et al. 2023

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“…For this reason, several hypotheses including cholinergic hypothesis, amyloid cascade hypothesis, tau protein hypothesis, oxidative stress hypothesis, bio-metals dyshomeostasis hypothesis, innate immune hypothesis, Osaka mutation and others have been proposed in an attempt to understand and explain the disease real pathogenesis [6][7][8]. From the cholinergic hypothesis point of view [9,10], elevating the essential neurotransmitter acetyl choline (ACh) levels through simultaneous inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) has great bene ts in dealing with the disease [11,12]. The AChE and BuChE are two hydrolytic enzymes responsible for termination of ACh action at synapse by cleaving Ach to choline and acetate moiety.…”

Section: Introductionmentioning

confidence: 99%

“…cyclohexanones, cyclopentanone, and 1-methylpiperidin-4-one to afford fourteen new compounds. All new compounds were screened against their acetylcholinesterase, butyrylcholinesterase and β-amyloid protein inhibition.In acetylcholinesterase inhibition assay, compound 3,7-Dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo [4,5]thieno[2,3-b]quinolin-11-amine (2h) showed IC 50 value 9.24 ± 0.01 µM x10 − 2 excelling tacrine itself.Compound 1,7- 2,3,4,7,8,9,5]thieno [2,3-b]quinolin-11-amine (2e) possessed excellent IC 50 values 0.58 ± 0.02 µM x10 − 2 and 0.51 ± 0.001 µM x10 − 4 for both the butyrylcholinesterase and β-amyloid protein inhibition assays, sequentially. In silico ADME studies were investigated for the promising members (octahydrobenzo-thienoquinolines 2c, 2d, 2e, 2h, 2i, and octahydropyrido-thienoquinolines 4e) and all the results were illustrated.…”

mentioning

confidence: 99%

“…Compound 1,7- 2,3,4,7,8,9,5]thieno [2,3-b]quinolin-11-amine (2e) possessed excellent IC 50 values 0.58 ± 0.02 µM x10 − 2 and 0.51 ± 0.001 µM x10 − 4 for both the butyrylcholinesterase and β-amyloid protein inhibition assays, sequentially. In silico ADME studies were investigated for the promising members (octahydrobenzo-thienoquinolines 2c, 2d, 2e, 2h, 2i, and octahydropyrido-thienoquinolines 4e) and all the results were illustrated.…”

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confidence: 99%

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New Tetracyclic Systems Integrated Thienopyridine Scaffold As An Anti-Dementia Lead: In Silico Study And Biological Screening

Mahmoud

Mohamed

et al. 2022

Preprint

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Alzheimer’s disease (AD) is a multifactorial incurable neurodegenerative disorder. To date, cholinesterase inhibitors (ChEI) are the mainstay line of treatment to ameliorate the symptoms of AD. Tacrine and donepezil are considered two important cornerstones as anti-dementia drugs with potent inhibitory effects. Accordingly, novel series of hexahydrobenzo-thienocyclopentapyridines, octahydrobenzo-thienoquinolines, hexahydrocyclopenta-(thienoquinoline/thienodipyridine) and octahydropyrido-thienoquinolines were efficiently synthesized from readily available reagents e.g. cyclohexanones, cyclopentanone, and 1-methylpiperidin-4-one to afford fourteen new compounds. All new compounds were screened against their acetylcholinesterase, butyrylcholinesterase and β-amyloid protein inhibition. In acetylcholinesterase inhibition assay, compound 3,7-Dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[4, 5]thieno[2,3-b]quinolin-11-amine (2h) showed IC50 value 9.24 ± 0.01 µM x10− 2 excelling tacrine itself. Compound 1,7-Dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[4, 5]thieno[2,3-b]quinolin-11-amine (2e) possessed excellent IC50 values 0.58 ± 0.02 µM x10− 2 and 0.51 ± 0.001 µM x10− 4 for both the butyrylcholinesterase and β-amyloid protein inhibition assays, sequentially. In silico ADME studies were investigated for the promising members (octahydrobenzo-thienoquinolines 2c, 2d, 2e, 2h, 2i, and octahydropyrido-thienoquinolines 4e) and all the results were illustrated. A comparative docking study was conducted between the promising members and both tacrine and donepezil in both acetyl and butyryl choline active sites. The results revealed extra binding patterns and good agreement with the biological results.

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New tetracyclic systems integrated thienopyridine scaffold as an anti-dementia lead: in silico study and biological screening

Mahmoud

Mohamed

et al. 2023

Med Chem Res

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Alzheimer’s disease (AD) is a multifactorial incurable neurodegenerative disorder. To date, cholinesterase inhibitors (ChEI) are the mainstay line of treatment to ameliorate the symptoms of AD. Tacrine and donepezil are considered two important cornerstones of anti-dementia drugs. Accordingly, novel series of hexahydrobenzothienocyclopentapyridines, octahydrobenzo-thienoquinolines, hexahydrocyclopenta(thienoquinoline/thienodipyridine), and octahydropyrido-thienoquinolines were efficiently synthesized from readily available reagent, e.g. cyclohexanones, cyclopentanone, and 1-methyl-piperidin-4-one to afford 14 new compounds. All new compounds were screened against their acetylcholinesterase, butyrylcholinesterase, and β-amyloid protein inhibition. In AChE inhibition assay, compound 3,7-dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[4,5]thieno[2,3-b]quinolin-11-amine (2h) showed IC50 value 9.24 ± 0.01 μM × 10−2 excelling tacrine. Compound 1,7-dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[4,5]thieno[2,3-b]quinolin-11-amine (2e) possess excellent IC50 values 0.58 ± 0.02 μM × 10−2 and 0.51 ± 0.001 μM × 10−4 for both butyrylcholinesterase and β-amyloid protein inhibition assays, sequentially. In silico ADME studies were investigated for the promising members (octahydrobenzo-thienoquinolines 2c, 2d, 2e, 2h, 2i, and octahydropyrido-thienoquinolines 4e) and all the results were illustrated. A comparative docking study was conducted between the promising members and both tacrine and donepezil in both acetyl and butyryl choline active sites. The results revealed extra binding patterns and good agreement with the biological results.

show abstract

Role of Acetylcholinesterase Inhibitors and Alzheimer Disease

Cited by 9 publications

References 153 publications

In Vitro Antiviral Effect and Potential Neuroprotection of Salvadora persica L. Stem Bark Extract against Lipopolysaccharides-Induced Neuroinflammation in Mice: LC-ESI-MS/MS Analysis of the Methanol Extract

In Vitro Antiviral Effect and Potential Neuroprotection of Salvadora persica L. Stem Bark Extract against Lipopolysaccharides-Induced Neuroinflammation in Mice: LC-ESI-MS/MS Analysis of the Methanol Extract

New Tetracyclic Systems Integrated Thienopyridine Scaffold As An Anti-Dementia Lead: In Silico Study And Biological Screening

New tetracyclic systems integrated thienopyridine scaffold as an anti-dementia lead: in silico study and biological screening

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