- Design, synthesis, and biological evaluation of novel N-Benzyl piperidine derivatives as potent HDAC/AChE inhibitors for Alzheimer's disease. [Journal Article]Bioorg Med Chem. 2023 Jan 21; 80:117178.BM
- The multitarget-directed ligands approach represents a potential strategy to provide effective treatments for Alzheimer's disease (AD) given its multifactorial pathology. Herein, a series of N-benzyl piperidine derivatives were designed, synthesized, and biologically characterized for dual inhibitions of histone deacetylase (HDAC) and acetylcholinesterase (AChE). Among the compounds tested, d5 an…
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- Dual-target ligand discovery for Alzheimer's disease: triphenylphosphoranylidene derivatives as inhibitors of acetylcholinesterase and β-amyloid aggregation. [Journal Article]
- Alzheimer disease (AD) is one of the major neurodegenerative diseases that could not be prevented or completely cured and may lead to death. Here, we target AChE and β-amyloid proteins. Synthesising new triphenylphosphporanylidene derivatives based on the surveyed literature and testing their biological activity revealed promising results especially for the acetyl triphenylphosphoranylidene deriv…
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- Effects of 3R, 16S-2-hydroxyethyl apovincaminate (HEAPO), donepezil and galantamine on learning and memory retention in naïve Wistar rats. [Journal Article]Acta Pharm. 2023 Mar 01; 73(1):91-105.AP
- The effects of 3R,16S-2-hydroxyethyl apovincaminate (HEAPO, RGH-10885) compared with those of two cholinesterase inhibitors, donepezil and galantamine, were examined in naïve Wistar rats using standard active and passive avoidance tests. The active avoidance test (shuttle box) and two passive avoidance tests (step-through and step-down) were performed according to the experimental design. There w…
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- Magnoflorine-Loaded Chitosan Collagen Nanocapsules Ameliorate Cognitive Deficit in Scopolamine-Induced Alzheimer's Disease-like Conditions in a Rat Model by Downregulating IL-1β, IL-6, TNF-α, and Oxidative Stress and Upregulating Brain-Derived Neurotrophic Factor and DCX Expressions. [Journal Article]
- Dementia or the loss of cognitive functioning is one of the major health issues in elderly people. Alzheimer's disease (AD) is one of the common forms of dementia. Treatment chiefly involves the use of acetylcholinesterase (AChE) inhibitors in AD. However, oxidative stress has also been found to be involved in the proliferation of the disease. Magnoflorine is one of the active compounds of Coptid…
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- Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis. [Systematic Review]J Alzheimers Dis. 2023 Jan 20 [Online ahead of print]JA
- CONCLUSIONS: α-GPC alone or in combination with donepezil improved cognition, behavior, and functional outcomes among patients with neurological conditions associated with cerebrovascular injury.
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- Indene-Derived Hydrazides Targeting Acetylcholinesterase Enzyme in Alzheimer's: Design, Synthesis, and Biological Evaluation. [Journal Article]
- As acetylcholinesterase (AChE) plays a crucial role in advancing Alzheimer's disease (AD), its inhibition is a promising approach for treating AD. Sulindac is an NSAID of the aryl alkanoic acid class, consisting of a indene moiety, which showed neuroprotective behavior in recent studies. In this study, newer Indene analogs were synthesized and evaluated for their in vitro AChE inhibition. Additio…
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- Characterization of Orange Peel Extract and Its Potential Protective Effect against Aluminum Chloride-Induced Alzheimer's Disease. [Journal Article]
- Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Hence, developing an effective treatment or protective agent is crucial for public health. The present study aims to characterize orange peel extract (OPE) through in vitro and in silico studies. Furthermore, it examines the protective effect of OPE against experimentally-induced Alzheimer's disease in rats. The …
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- Synthesis, DFT Studies, Molecular Docking and Biological Activity Evaluation of Thiazole-Sulfonamide Derivatives as Potent Alzheimer's Inhibitors. [Journal Article]
- Alzheimer's disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer's treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer'…
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- Influence of Sex and Muscarinic Activity on Memory Retrieval in Mouse Model of Traumatic Brain Injury. [Journal Article]
- Traumatic brain injury (TBI) is a serious global risk factor leading to the onset of cognitive impairment and neurodegenerative diseases. Cognitive and memory impairment following a TBI is associated with the dysregulation of cholinergic neurotransmission in the brains of subjects. The extent of memory impairment following a TBI is linked with the sex of the subject. This study aimed to identify …
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- M1/M4-Preferring Muscarinic Cholinergic Receptor Agonist Xanomeline Reverses Wake and Arousal Deficits in Nonpathologically Aged Mice. [Journal Article]ACS Chem Neurosci. 2023 Jan 19 [Online ahead of print]AC
- Degeneration of the cholinergic basal forebrain is implicated in the development of cognitive deficits and sleep/wake architecture disturbances in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Indirect-acting muscarinic cholinergic receptor agonists, such as acetylcholinesterase inhibitors (AChEIs), remain the only FDA-approved treatments for the cognitive impairments observed in …
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- Acetylcholinesterase inhibition of Alzheimer's disease: identification of potential phytochemicals and designing more effective derivatives to manage disease condition. [Journal Article]J Biomol Struct Dyn. 2023 Jan 18 [Online ahead of print]JB
- Alzheimer's disease (AD) is a brain disease characterized by gradual memory loss and cognitive impairments. Acetylcholinesterase (AChE) inhibitors-such as donepezil, memantine, and tacrine-are FDA-approved medications for AD treatment. Due to the lack of their efficacy and higher side effects, many researchers have been searching for effective and safer alternatives. In this study, experimentally…
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- Lipopolysaccharide induced neuroprotective effects of bacterial protease against Alzheimer's disease in male Wistar albino rats. [Journal Article]Int J Biol Macromol. 2023 Jan 12 [Online ahead of print]IJ
- Alzheimer's disease (AD) is a highly severe neurodegenerative condition that affects the hippocampus and is characterized by memory loss and dementia. This investigation aims to determine the potential of a bacterial protease enzyme produced by a new mutant strain of bacteria (Bacillus cereus S6-3/UM90) to influence the rat behavioural, biochemical, histological, and immuno-histochemical function…
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- Chinese herbal compound Jinsiwei improves synaptic plasticity in mice with sporadic Alzheimer's disease induced by streptozotocin. [Journal Article]J Tradit Chin Med. 2023 Feb; 43(1):78-86.JT
- CONCLUSIONS: Jinsiwei can alleviate learning and memory impairments in a mouse model of SAD, increase the number of synapses and enhance synaptic plasticity rescuing the expression of drebrin, syn, and NR2B and inhibiting cofilin expression.
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- Rationally designed donepezil-based hydroxamates modulate Sig-1R and HDAC isoforms to exert anti-glioblastoma effects. [Journal Article]Eur J Med Chem. 2023 Jan 02; 248:115054.EJ
- The pursuit of activating the HDAC inhibitory template towards additional mechanisms spurred us to design dual modulators (Sig-1R agonist - HDAC inhibitor) via utilization of the core structural unit of donepezil (an FDA-approved anti-Alzheimer's agent) as a surface recognition part. Literature precedents coupled with our experience rendered us with several insights that led to the inclusion of c…
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- The measured CSF/plasma donepezil concentration ratio but not individually measured CSF and plasma concentrations significantly increase over 24 h after donepezil treatment in patients with Alzheimer's disease. [Journal Article]Biomed Pharmacother. 2023 Jan 09; 159:114223.BP
- CONCLUSIONS: The measurement of the CSF/plasma donepezil concentration ratio could be used to better evaluate the optimal dose of donepezil.
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- New cyclopentaquinoline and 3,5-dichlorobenzoic acid hybrids with neuroprotection against oxidative stress for the treatment of Alzheimer's disease. [Journal Article]
- Alzheimer's disease (AD) is a progressive neurodegenerative brain disease. Thus, drugs including donepezil, rivastigmine, and galantamine are not entirely effective in the treatment of this multifactorial disease. The present study evaluates eight derivatives (3a-3h) as candidates with stronger anti-AD potential but with less side effects. Reactive oxygen species (ROS) assays were used to assess …
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- Design, synthesis, spectroscopic characterizations, single crystal X-ray analysis, in vitro xanthine oxidase and acetylcholinesterase inhibitory evaluation as well as in silico evaluation of selenium-based N-heterocyclic carbene compounds. [Journal Article]J Biomol Struct Dyn. 2023 Jan 09 [Online ahead of print]JB
- Herein, eight new NHC-based selenourea derivatives were synthesized and characterized by using spectroscopic method (1H, 19F, and 13C NMR, FT-IR), and elemental analysis techniques. These compounds were synthesized by mixing benzimidazolium salts, potassium carbonate, and selenium powder in ethyl alcohol. Additionally, the molecular and crystal structures of the three compounds (1c, 2b, and 2c) w…
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- Comprehensive metabolomics and lipidomics profiling uncovering neuroprotective effects of Ginkgo biloba L. leaf extract on Alzheimer's disease. [Journal Article]
- Introduction: Ginkgo biloba L. leaf extract (GBLE) has been reported to be effective for alleviating cognitive and memory impairment in Alzheimer's disease (AD). Nevertheless, the potential mechanism remains unclear. Herein, this study aimed to explore the neuroprotective effects of GBLE on AD and elaborate the underlying therapeutic mechanism. Methods: Donepezil, the most widely prescribed drug …
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- Ursolic acid and rosmarinic acid ameliorate alterations in hippocampal neurogenesis and social memory induced by amyloid beta in mouse model of Alzheimer's disease. [Journal Article]
- Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder characterized by substantial neuronal damage which manifests in the form of deficits in memory and cognition. In spite of the debilitating nature of Alzheimer's disease (AD), a dearth of treatment strategies calls for the need to develop therapeutic agents that stimulate neurogenesis and alleviate the associated cognitive defic…
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- Euonymus alatus Twig Extract Protects against Scopolamine-Induced Changes in Brain and Brain-Derived Cells via Cholinergic and BDNF Pathways. [Journal Article]
- In the current study, the therapeutic and preventive effects of Euonymus alatus (EA) twig extract were investigated in a mouse model of cognitive deficit and B35 cells. Twig extract 1 was extracted with 70% ethanol and later twig extract 2 was extracted through liquid-liquid extraction with 70% ethanol and hexane. EA twig 2 (300 mg/kg) along with the standard drug donepezil (5 mg/kg) were orally …
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- Rapidly Progressive Frontotemporal Dementia With Amyotrophic Lateral Sclerosis in an Elderly Female. [Case Reports]Cureus. 2022 Dec; 14(12):e32182.C
- A 69-year-old female with a family history significant for early onset dementia and a past medical history significant for coronary artery disease, primary hypertension, type two diabetes mellitus, and Crohn's disease presents to our facility with rapidly progressive cognitive decline, delusions, hallucinations, and ambulatory dysfunction over the past two months. Neurological examination was rem…
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- Anti-dementia drugs: a descriptive study of the prescription pattern in Italy. [Journal Article]
- CONCLUSIONS: To our knowledge, this study represents the first attempt to investigate the ADD prescription pattern in Italy with a Public Health approach. In 2019, the proportion of ADD private purchases point out several issues concerning the reimbursability of ADDs. From a regulatory perspective, ADDs can be reimbursed by the National Health System only to patients diagnosed with AD; therefore, the off-label use of ADDs in patients with mild cognitive impairment may partially explain this phenomenon. The study extends knowledge on the use of ADDs, providing comparisons with studies from other countries that investigate the prescription pattern of ADDs.
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- Natural inhibitors for acetylcholinesterase and autophagy modulators as effective antagonists for tau and β-amyloid in Alzheimer's rat model. [Journal Article]Biomarkers. 2023 Jan 03 [Online ahead of print]B
- Background: Phytochemicals have amazing biological effects in relation to age-related illnesses and are increasingly being studied in clinical trials. The goal of this study was to examine the effectiveness of the aqueous extracts of Rosmarinus officinalis L. (Rosemary) and Crocus sativus L. (Saffron) and their combinations as tau and β-amyloid antagonists in an Alzheimer's rat model. Methods: Al…
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- Review of Alzheimer's disease drugs and their relationship with neuron-glia interaction. [Review]
- Alzheimer's disease (AD) is the most common cause of dementia worldwide. Because Alzheimer's disease has no known treatment, sufferers and their caregivers must concentrate on symptom management. Astrocytes and microglia are now known to play distinct physiological roles in synaptic function, the blood-brain barrier, and neurovascular coupling. Consequently, the search for drugs that can slow the…
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- Cognitive enhancing effects and anticholinesterase activity of stem bark and leaf extracts of Prunus africana. [Journal Article]
- Alzheimer's disease is ranked among the top five causes of death for old people. Globally, it is approximated that there are 7.7 million new cases of Alzheimer's disease per annum and it is expected that by the year 2050, as many as 1.5% of people will be victims of Alzheimers or other types of dementia. Currently there is no cure for Alzheimer's disease and the conventional therapeutics agents a…
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- Donepezil accelerates the release of PLGA microparticles via catalyzing the polymer degradation regardless of the end groups and molecular weights. [Journal Article]Int J Pharm. 2022 Dec 28; 632:122566.IJ
- Poly (lactic-co-glycolic acid) (PLGA) is one of the most successful polymers for sustained parenteral drug products in the market. However, rational selection of PLGA in the formulations is still challenging due to the lack of fundamental studies. The present study aimed to investigate the influence of donepezil (DP) on the in-vitro and in-vivo performance of PLGA sustained microspheres. Three ki…
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- Role of multi-targeted bioactive natural molecules and their derivatives in the treatment of Alzheimer's disease: an insight into structure-activity relationship. [Review]J Biomol Struct Dyn. 2022 Dec 29 [Online ahead of print]JB
- Alzheimer's disease (AD) is a complex neurodegenerative disorder involving cognitive dysfunction like short-term memory and behavioral changes as the disease progresses due to other unaltered physiological factors. The solution for this problem is Multi-targeted Drugs (MTDs), which can affect multiple determinants to realize the multifunctional effects. Acetylcholinesterase (AChE) inhibitors done…
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- Two new iridoids and triterpenoid analogues from the leaves of Viburnum chingii and their anti-acetylcholinesterase activity. [Journal Article]Fitoterapia. 2022 Dec 23; 165:105400.F
- Two undescribed split-ring iridoids (1-2) with six known triterpenes (3-8) and one steride (9) were isolated from the Viburnum chingii. Compound 2 possessed an unprecedented split-ring iridoid skeleton formed by electrocyclic reaction and split ring. The structures and absolute configurations of the new iridoids were established by NMR, HRESIMS, and ECD calculations. All the isolated compounds we…
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- Design, Synthesis, and In Vitro and In Silico Approaches of Novel Indanone Derivatives as Multifunctional Anti-Alzheimer Agents. [Journal Article]
- Alzheimer's disease (AD) is a neurological, progressive illness that typically affects the elderly and is clinically distinguished by memory and cognitive decline. Due to a number of factors, including the absence of a radical treatment, an increase in the patient population over time, the high cost of care and treatment, and a significant decline in patients' quality of life, the importance of t…
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- Discovery of pyrrole derivatives as acetylcholinesterase-sparing butyrylcholinesterase inhibitor. [Journal Article]
- Inspired by the crucial roles of (hetero)aryl rings in cholinesterase inhibitors and the pyrrole ring in new drug discovery, we synthesized 19 pyrrole derivatives and investigated their cholinesterase inhibitory activity. As a result, compounds 3o, 3p, and 3s with a 1,3-diaryl-pyrrole skeleton showed high selectivity toward BChE over AChE with a best IC50 value of 1.71 ± 0.087 µM, which were comp…
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