Synthesis and efficacy of 1-[bis(4-fluorophenyl)-methyl]piperazine derivatives for acetylcholinesterase inhibition, as a stimulant of central cholinergic neurotransmission in Alzheimer’s disease

2006 ◽  
Vol 16 (15) ◽  
pp. 3932-3936 ◽  
Author(s):  
C.T. Sadashiva ◽  
J.N. Narendra Sharath Chandra ◽  
K.C. Ponnappa ◽  
T. Veerabasappa Gowda ◽  
Kanchugarakoppal S. Rangappa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Acetylcholinesterase Inhibition ◽  
Cholinergic Neurotransmission ◽  
Piperazine Derivatives

scholarly journals Medicinal Plants from Northeastern Brazil against Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Alexandre Batista Penido ◽  
Selene Maia De Morais ◽  
Alan Bezerra Ribeiro ◽  
Daniela Ribeiro Alves ◽  
Ana Livya Moreira Rodrigues ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant Activity ◽  
Phenolic Compounds ◽  
Antioxidant Activities ◽  
Mangifera Indica ◽  
Psidium Guajava ◽  
Northeastern Brazil ◽  
Acetylcholinesterase Inhibition ◽  
Copaifera Langsdorffii

Alzheimer’s disease (AD) has been linked with oxidative stress, acetylcholine deficiency in the brain, and inflammatory processes. In the northeast region of Brazil, various plants are used to treat several diseases associated with these processes; then an antioxidant test was performed with those plants in a previous work and twelve species with higher antioxidant activity were selected for AChE inhibition evaluation. The phenolic compounds content was determined by Folin–Ciocalteu test and flavonoid content with AlCl3reagent using UV-visible spectrophotometry. The antioxidant activity was assessed analyzing the inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS) and by theβ-carotene/linoleic acid system and acetylcholinesterase inhibition using qualitative and quantitative tests. The combination of better acetylcholinesterase inhibitory and antioxidant activities pointed out six species, in descending order, as the best potential sources of therapeutic agents against AD:Hancornia speciosa > Myracrodruon urundeuva > Copaifera langsdorffii > Stryphnodendron coriaceum > Psidium guajava > Mangifera indica. Besides, the phenolic compounds in the species probably contribute to these activities. However, further pharmacological studies to assess the specific applications of these plants against AD are required to confirm these results.

scholarly journals The Therapeutic Potential of Berberis darwinii Stem-Bark: Quantification of Berberine and In Vitro Evidence for Alzheimer's Disease Therapy

2011 ◽  
Vol 6 (8) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Solomon Habtemariam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Charles Darwin ◽  
Potent Inhibitor ◽  
Methanolic Extract ◽  
Therapeutic Potential ◽  
Stem Bark ◽  
Acetylcholinesterase Inhibition ◽  
Disease Therapy

Berberis darwinii is native to South America but has been widely distributed in Europe and other continents following its discovery by Charles Darwin. Herewith, the therapeutic potential of stem-bark of the plant for treating Alzheimer's disease was studied using an in vitro acetylcholinesterase inhibition assay. It was found that the methanolic extract of the stem-bark was a potent inhibitor of the enzyme with an IC50 value of 1.23 ± 0.05 μg/mL. An HPLC-based berberine quantification study revealed an astonishing 38% yield of the dried methanolic extract.

scholarly journals Pharmacokinetic and Pharmacodynamic Evaluation of Nasal Liposome and Nanoparticle Based Rivastigmine Formulations in Acute and Chronic Models of Alzheimer’s Disease

2021 ◽  
Author(s):  
Sampath Kumar L Rompicherla ◽  
Karthik Arumugam ◽  
Sree Lalitha Bojja ◽  
Nitesh Kumar ◽  
Mallikarjuna Rao Chamallamudi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
Rapid Onset ◽  
Liposomal Formulation ◽  
Direct Access ◽  
Acetylcholinesterase Inhibition ◽  
Pharmacokinetic Parameters ◽  
Ageing Population ◽  
Onset Of Action

Abstract With the increasing ageing population and progressive nature of the disease, Alzheimer's disease (AD) poses to be an oncoming epidemic with limited therapeutic strategies. It is characterized by memory loss, behavioral instability, impaired cognitive function, predominantly, cognitive inability manifested due to the accumulation of β-amyloid, with malfunctioned cholinergic system. Rivastigmine, a reversible dual cholinesterase inhibitor is more tolerable and widely used choice of drug for AD. However, rivastigmine being hydrophilic and undergoing first pass metabolism, exhibits low CNS bioavailability. Nanoformulations including liposomes and PLGA nanoparticles can encapsulate hydrophilic drugs and deliver efficiently to brain. Besides, the nasal route is receiving considerable attention recently, due to its direct access to brain. Therefore, the present study attempts to evaluate the pharmacokinetic and pharmacodynamic properties of nasal liposomal and PLGA nanoparticle formulations of rivastigmine in scopolamine induced amnesia model and validate the best formulation by employing pharmacokinetic and pharmacodynamic (PK-PD) modelling. Nasal liposomal rivastigmine formulation showed the best pharmacokinetic features with rapid onset of action (Tmax=5 minutes), higher Cmax (1489.5 ± 620.71), enhanced systemic bioavailability (F=118.65 ± 23.54; AUC= 35921.75 ± 9559.46), increased half-life (30.92 ± 8.38 minutes), and reduced clearance rate (Kel (1/min) = 0.0224 ± 0.006) compared to oral rivastigmine (Tmax= 15 minutes; Cmax= 56.29 ± 27.05; F=4.39 ± 1.82; AUC=1663.79 ± 813.54; t1/2= 13.48 ± 5.79; Kel (1/min) =0.0514 ± 0.023). Further, the liposomal formulation significantly rescued the memory deficit induced by scopolamine superior to other formulations as assessed in Morris water maze and passive avoidance tasks. PK-PD modelling demonstrated strong correlation between the pharmacokinetic parameters and acetylcholinesterase inhibition of liposomal formulation.

scholarly journals Fighting paralysis and dementia: Acetylcholinesterase inhibitors and reactivators in therapy

2010 ◽  
Vol 32 (4) ◽  
pp. 18-23
Author(s):  
Zoran Radi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Myasthenia Gravis ◽  
Acetylcholinesterase Inhibitors ◽  
Ache Inhibitors ◽  
Cholinergic Neurotransmission ◽  
Key Enzyme

Inhibition of acetylcholinesterase (AChE; EC 3.1.1.7), one of most efficient known enzymes and a key enzyme of cholinergic neurotransmission, can be therapeutically beneficial, primarily in the treatment of Alzheimer's disease, myasthenia gravis and in ophthalmology. In this article, several therapeutic AChE inhibitors and the mechanism of their interaction with AChE are summarized.

Design and Microwave-Assisted Synthesis of Aza-Resveratrol Analogs with Potent Cholinesterase Inhibition

2020 ◽  
Vol 19 (8) ◽  
pp. 630-641
Author(s):  
Brunella Biscussi ◽  
Victoria Richmond ◽  
Carlos Javier Baier ◽  
Pau Arroyo Mañez ◽  
Ana Paula Murray
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Modeling ◽  
Cholinesterase Inhibitors ◽  
Natural Compounds ◽  
Acetylcholinesterase Inhibition ◽  
Cholinesterase Inhibition ◽  
Anionic Site ◽  
Microwave Assisted ◽  
Resveratrol Analogs

Background: Currently approved Alzheimer’s disease medications mainly comprise acetylcholinesterase inhibitors. Many of these inhibitors are either natural compounds or synthetic molecules inspired in natural compounds. Hybrid molecules that can interact with different target sites of the enzyme could lead to the discovery of effective multitarget drugs. Objective: To design, synthesize, and evaluate a series of new aza-resveratrol analogs as in vitro acetyl- and butyrylcholinesterase inhibitors. Methods: The synthesis is achieved by a simple and efficient microwave-assisted method, from commercially available starting materials. Compounds are designed as hybrids of an aza-stilbene nucleus (Schiff base) connected to a tertiary amine by a hydrocarbon chain of variable length, designed to interact both with the peripheric anionic site and the catalytic site of the enzyme. Results: All the derivatives inhibit both enzymes in a concentration-dependent manner, acting as moderate to potent cholinesterase inhibitors. The most potent inhibitors are compounds 12b (IC50 = 0.43 μM) and 12a (IC50 = 0.31 μM) for acetyl- and butyrylcholinesterase, respectively. Compounds 12a and 12b also exhibit significant acetylcholinesterase inhibition in SH-SY5Y human neuroblastoma cells without cytotoxic properties. Enzyme kinetic studies and molecular modeling reveal that inhibitor 12b targets both the catalytic active site and the peripheral anionic site of acetylcholinesterase what makes it able to modulate the self-induced β-amyloid aggregation. Furthermore, the molecular modeling analysis helps to assess the impact of the linker length in the inhibitory activity of this family of new cholinesterase inhibitors. Conclusion: These compounds have the potential to serve as a dual binding site inhibitor and might provide a useful template for the development of new anti-Alzheimer’s disease agents.

Xanthone: Potential Acetylcholinesterase Inhibitor for Alzheimer's Disease Treatment

2021 ◽  
Vol 21 ◽  
Author(s):  
Vincentsia Vienna Vanessa ◽  
Siau Hui Mah
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Acetylcholinesterase Inhibitor ◽  
Structure Activity Relationship ◽  
Acetylcholinesterase Inhibition ◽  
Activity Relationship ◽  
Structure Activity ◽  
Hydrophobic Moiety

: Alzheimer's disease is a neurodegenerative disorder that results in progressive and irreversible central nervous system impairment, which has become one of the severe issues recently. The most successful approach of Alzheimer’s treatment is the administration of cholinesterase inhibitors to prevent the hydrolysis of acetylcholine and subsequently improve the cholinergic postsynaptic transmission. This review highlights a class of heterocycle, namely xanthone and its remarkable acetylcholinesterase inhibitory activities. Naturally occurring xanthones, including oxygenated, prenylated, pyrano and glycosylated xanthones exhibited promising inhibition effects towards acetylcholinesterase. Interestingly, synthetic xanthone derivatives with complex substituents such as alkyl, pyrrolidine, piperidine and morpholine have shown greater acetylcholinesterase inhibition activities. Structure-activity relationship of xanthones revealed that the type and position of substituent(s) attached to the xanthone moiety influenced their acetylcholinesterase inhibition activities where hydrophobic moiety will lead to an improved activity by contributing the π-π interactions, as well as the hydroxy substituent(s) by forming hydrogen-bond interactions. Thus, further studies including quantitative structure-activity relationship, in vivo and clinical validation studies are crucial for the development of xanthones into novel anti-Alzheimer's disease drugs.

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