Acetylcholinesterase Inhibitors Research Articles

Acetylcholinesterase (AChE) Insensitivity of Aedes aegypti Exposured by Citronella Oil (Cymbopogon nardus)

Aedes mosquitoes are vectors of viruses, namely the dengue virus. Treatment with insecticides is no longer effective if the target mosquito is resistant. Therefore, efforts are needed to overcome the resistance of these mosquitoes. Inhibition of the enzyme acetylcholinesterase (AChE) is one way the synthetic insecticide Profenofos works; if AChE is inhibited, acetylcholine accumulation will disrupt the nervous system. Insensitivity to AChE is one mechanism of mosquito resistance to insecticides. Based on this, the problem is formulated as follows: is the increase in susceptibility of Aedes aegypti mosquitoes to alphacymethrin, citronella oil, and a combination of both caused by a decrease in the insensitivity of mosquito AChE? This study aims to determine the AChE insensitivity of Aedes aegypti mosquitoes to citronella oil, a combination of citronella oil and alphacymethrin 0.03%), compared to the positive control (insecticide alphacymethrin 0.03%). Percentage of mosquito mortality after being held for 24 hours: The results showed no difference between the two groups of mosquitoes without treatment (A) and 100 µL/L citronella oil (B), F count 0.000, Sig. 1.000, significance value <0.05. Exposure to 100 µL/L citronella oil on instar III-IV mosquito larvae did not make mosquitoes more susceptible or more resistant to 0.03% alphacypermethrin insecticide. Based on the absorption value analysis results using the T-test between group A/ without treatment and group B with 100µL/L citronella oil treatment showed a Sig. (2-tailed) value of 0.547>0.05 means there is no significant difference between the two groups.

Exploring the Therapeutic Potential of 8-Prenyldaidzein: A Comprehensive Study of its Multi-Target Efficacy in Alzheimer's Disease.

Alzheimer's disease (AD) is marked by cognitive decline, amyloid plaques, neurofibrillary tangles, and cholinergic loss. Due to the limited success of amyloid-targeted therapies, attention has shifted to new non-amyloid targets like phosphodiesterases (PDE). This study investigates the potential of Flemingia vestita (FV) phytomolecules and derivatives, particularly 8-Prenyldaidzein, in AD treatment. Phytocompounds and derivatives were screened for drug-likeness, toxicity, BBB permeability, and ADME profiles. Molecular docking was conducted with PDE5A, BACE-1, and AChE, followed by molecular dynamics (MD) simulations on the best binding complexes. 8-Prenyldaidzein, a derivative of daidzein, demonstrated favorable drug-likeness and ADME properties. It exhibited strong binding to PDE5A, BACE-1, and AChE, with MD simulations confirming stable protein-ligand interactions. The multi-target potential of 8-Prenyldaidzein, particularly through non-amyloid pathways, offers a promising approach to AD therapy. Its inhibition of PDE5A, BACE-1, and AChE could address multiple aspects of AD pathology. 8-Prenyldaidzein shows strong potential as a multi-target inhibitor for AD treatment. While in-silico findings are promising, further experimental validation is needed to confirm its clinical applicability.

SYNTHESIS, CHARACTERIZATION AND CHOLINESTERASE INHIBITORY EFFECTS OF IBUPROFEN-BASED SPIROTHIAZOLIDINONES

Objective: A novel class of spirothiazolidinone derivatives were designed, synthesized, and assessed as possible acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors for Alzheimer's disease therapy. Material and Method: In this study, novel spirocyclic compounds were synthesized by one-pot reaction. IR, 1H NMR, 13C NMR, LC-MS and elemental analysis techniques have all been used to clarify the chemical structures of the compounds. AChE and BuChE inhibitory effects of compounds (4a-e and, 5a-e) were assayed according to Ellman’s method using galantamine as reference. Result and Discussion: According to the inhibition data, compound 4e demonstrated the most promising activity against AChE, with an IC50 value of 39.53±1.94 µM, while compound 4b exhibited the most potential against BuChE, with an IC50 value of 95.97±1.79 µM.

Hydroxyl chalcone derivative DK02 as a multi-target-directed ligand for Alzheimer's disease: A preclinical study in zebrafish.

Alzheimer's disease (AD) is a widespread neurodegenerative condition characterized by amyloid-beta (Aβ) plaques and tau protein aggregates, leading to significant cognitive decline. Existing treatments primarily offer symptomatic relief, underscoring the urgent need for novel therapies that address multiple AD pathways. This study evaluates the efficacy of DK02, a hydroxyl chalcone derivative, in a scopolamine-induced dementia model in zebrafish, hypothesizing that it targets several neurodegenerative mechanisms simultaneously. We employed a blend of experiments, including in silico docking, in vitro enzyme inhibition assays and in vivo zebrafish models, to assess therapeutic effects of DK02. Methods included molecular docking to forecast interaction sites, acetylcholinesterase (AChE) inhibition testing, and various behavioural and histopathological analyses to gauge DK02's cognitive and neuroprotective impacts. DK02 emerged as a potent AChE inhibitor via virtual screening, and significantly enhanced cognitive functions in zebrafish, by improving memory retention and reducing anxiety-like behaviours. DK02 also displayed strong antioxidant properties, reducing oxidative stress-induced neuronal damage. Histopathological analysis confirmed its neuroprotective effects by showing decreased amyloid plaque burden and mitigated structural brain damage. DK02 shows promise as a multi-target-directed ligand for AD, offering a new therapeutic path by simultaneously addressing cholinergic, oxidative and amyloid pathways. Its potential to enhance cognitive functions and curtail neurodegeneration suggests advantages over current symptomatic treatments. Further research into DK02 mechanisms and long-term impacts is essential for its development in AD therapy.

Anticholinesterase Activity and Bioactive Compound Profiling of Six Hop (Humulus lupulus L.) Varieties.

Hops (Humulus lupulus L.) are widely recognized for their use in brewing, but they also possess significant pharmacological properties due to their rich bioactive compounds, with many varieties exhibiting diverse characteristics. This study investigates the chemical composition and biological activities of extracts from six hop varieties, focusing on quantifying xanthohumol and lupulone using High-Performance Liquid Chromatography (HPLC) and Total Phenolic Content (TPC) analysis. The hop varieties demonstrated significant variability in bioactive compound concentrations, with Aurora showing the highest xanthohumol (0.665 mg/g) and Zwiegniowski the highest lupulone (9.228 mg/g). TPC analysis revealed Aurora also had the highest phenolic content (22.47 mg GAE/g). Antioxidant activities were evaluated using DPPH, ABTS, CUPRAC, and FRAP assays, with Aurora and Oregon Fuggle displaying the most potent capacities. Aurora, in particular, showed the highest activity across multiple assays, including significant acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase inhibition, with IC50 values of 24.39 mg/mL, 20.38 mg/mL, and 9.37 mg/mL, respectively. The chelating activity was also assessed, with Apolon demonstrating the strongest metal ion binding capacity (IC50 = 1.04 mg/mL). Additionally, Aurora exhibited the most effective hyaluronidase inhibition (IC50 = 10.27 mg/mL), highlighting its potential for anti-inflammatory applications. The results underscore the influence of genetic and environmental factors on the bioactive compound profiles of hop varieties and their biological activity offering promising avenues for pharmaceutical and nutraceutical applications. However, further studies are needed to fully understand the potential interactions between hop cones components.

Phytochemical and Cytotoxic Aspects of Amaryllidaceae Alkaloids in Galanthus Species: A Review.

The genus Galanthus (Amaryllidaceae) currently contains 25 plant species naturally occurring in Europe and the Middle East region. These perennial bulbous plants possess well-known medicinal and ornamental qualities. Alkaloid diversity is their most distinctive phytochemical feature. A total of 127 compounds (≈20% of all known Amaryllidaceae alkaloids) grouped in 16 structural types have been previously found in Galanthus extracts. Some structural types like galanthindole, graciline and plicamine were first discovered in Galanthus plants. Nine Galanthus species, however, remain unstudied regarding their alkaloid patterns. Intraspecific variability has only been studied in G. nivalis and G. elwesii. Amaryllidaceae alkaloids are molecules with anticholinesterase, antibacterial, antifungal, antiviral and anticancer properties. Galanthamine, isolated for the first time from Galanthus woronowii Losinsk., stands out as an acetylcholinesterase inhibitor approved for medical use by the FDA for the treatment of symptoms of Alzheimer's disease. Lycorine, narciclasine and pancratistatin are noteworthy cytotoxic and antitumor alkaloids. Structural types like galanthamine, homolycorine and haemanthamine are fairly well studied in anticancer research, but little to no information is available on galanthindole, graciline and other types. This review aims to present an update on the alkaloid diversity of Galanthus spp. and highlight the need for further research on the antitumor potential of these molecules.

Synthesis and characterisation of an acetylcholinesterase inhibitor

Synthesis and characterisation of an acetylcholinesterase inhibitor

Biological Implications of the Intrinsic Deformability of Human Acetylcholinesterase Induced by Diverse Compounds: A Computational Study.

The enzyme acetylcholinesterase (AChE) plays a crucial role in the termination of nerve impulses by hydrolyzing the neurotransmitter acetylcholine (ACh). The inhibition of AChE has emerged as a promising therapeutic approach for the management of neurological disorders such as Lewy body dementia and Alzheimer's disease. The potential of various compounds as AChE inhibitors was investigated. In this study, we evaluated the impact of natural compounds of interest on the intrinsic deformability of human AChE using computational biophysical analysis. Our approach incorporates classical dynamics, elastic networks (ENM and NMA), statistical potentials (CUPSAT and SWOTein), energy frustration (Frustratometer), and volumetric cavity analyses (MOLE and PockDrug). The results revealed that cyanidin induced significant changes in the flexibility and rigidity of AChE, especially in the distribution and volume of internal cavities, compared to model inhibitors such as TZ2PA6, and through a distinct biophysical-molecular mechanism from the other inhibitors considered. These findings suggest that cyanidin could offer potential mechanistic pathways for future research and applications in the development of new treatments for neurodegenerative diseases.

Structure-based virtual screening of Trachyspermum ammi metabolites targeting acetylcholinesterase for Alzheimer's disease treatment.

In recent decades, Alzheimer's disease (AD) has garnered significant attention due to its rapid global prevalence. The cholinergic hypothesis posits that the degradation of acetylcholine by acetylcholinesterase (AChE) contributes to AD development. Despite existing anti-AChE drugs, their adverse side effects necessitate new agents. This study analyzed 150 bioactive phytochemicals from Trachyspermum ammi using structure-based drug design and various in-silico tools to identify potent anti-AChE compounds. Compounds were screened for drug-likeness (QEDw ≥50%) and bioavailability (≥55%) and underwent toxicity profiling via the ProTox-II server. Selected compounds were prepared for molecular docking with the human AChE protein as the receptor. Viridifloral, 2-Methyl-3-glucosyloxy-5-isopropyl phenol, Alpha-Curcumene, and Sterol emerged as top candidates with high AChE affinity. These results were validated by molecular dynamics simulations, confirming stable interactions. The hit compounds were further evaluated for drug-likeness using Lipinski's rule and ADMET properties, confirming favorable pharmacokinetic profiles. DFT optimization analyzed frontier molecular orbitals and electrostatic potential, demonstrating favorable chemical reactivity and stability. This study suggests that these identified compounds could be novel nature-derived AChE inhibitors, potentially contributing to AD treatment. However, further in-vitro and in-vivo studies are necessary to confirm their efficacy in biological systems. Future research will focus on developing these compounds into safe and effective drugs to combat Alzheimer's disease.

Fenugreek Sprouts Around the World: Exploring Therapeutic and Nutritional Benefits.

This study investigates the therapeutic and nutritional potential of fenugreek sprouts from 30 diverse genotypes sourced from various regions. The aim was to characterize and compare their therapeutic attributes, including antioxidant capacity, antidiabetic, and anti-cholinesterase activities, along with their nutritional compositions, particularly minerals, and protein content. Results revealed significant variations among the genotypes in terms of their therapeutic properties. China genotypes exhibited notable α-amylase inhibition 64.57%, suggesting potential antidiabetic properties, while South Sudan genotypes demonstrated significant acetylcholinesterase (14.44%) and butyrylcholinesterase inhibitions, indicating possible cognitive health benefits. The Morocco and Konya/Türkiye genotypes exhibited noteworthy antioxidant effects, with showing DPPH • scavenging activities of 7.79% and 7.23%, and ABTS •+ activities of 27.87% and 27.31%, respectively. Mineral analysis revealed considerable differences across genotypes. Israel genotypes had the highest iron content (43.18 mg/100 g), Sivas/Türkiye genotype had the highest potassium levels (2259.87 mg/100 g), and Kayseri/Türkiye genotype had the highest sodium content (616.91 mg/100 g). Ukraine genotypes contained the most magnesium (266.61 mg/100 g), while Israel genotypes also had the highest zinc content (54.44 mg/100 g). The protein content of the fenugreek sprouts varied significantly, with Corum/Türkiye showing the highest protein content at 5.75/100 g. Principal component analysis (PCA) highlighted the relationships among the mineral nutrients and protein content, revealing distinct groupings of genotypes based on their mineral compositions. Correlation analysis further elucidated the associations between various minerals and protein content. In conclusion, this study underscores the potential therapeutic and nutritional significance of fenugreek sprouts.

Quantification of Bioactive Compounds by HPLC-ESI-MS/MS and Evaluation of Antioxidant and Enzyme Inhibitory Activities of Acorn Flour Extracts.

This study provides the first comprehensive evaluation of the bioactive potential of acorn flour extracts (Quercus robur, Fagaceae) prepared at different temperatures (20, 60, 80 and 100 °C), focusing on polyphenolic content, antioxidant properties and enzyme inhibitory activities. Through HPLC-ESI-MS/MS analysis, 36 bioactive compounds were identified, with the extract at 60 °C showing the highest concentrations of key polyphenols, notably gallic acid (210,008.9 mg·kg-1) and ellagic acid (45,469.6 mg·kg-1). This extract also exhibited a high antioxidant activity and significant inhibition of glucosidase and acetylcholinesterase, suggesting potential benefits for diabetes management and neuroprotection. The results indicate that extraction temperature affects bioactivity, with the 60 °C extract standing out as a promising candidate for nutraceutical, pharmaceutical, and cosmeceutical applications due to its rich polyphenol profile and potent biological properties.

Marine Natural Products as Novel Treatments for Alzheimer's Disease

Abstract: Alzheimer's disease is distinguished by gradual changes in behavior because of the aggregation of β-amyloid and τ protein that blocks the signal transduction pathway. It is one of the major problems in the current scenario. It mainly occurs after the age of 60 and eventually leads to memory loss. Nonetheless, medicinal plants have therapeutic potential to improve many diseases. Medicinal drugs with their phytoconstituents may offer therapeutic potential for improving the preventive treatment for Alzheimer's disease. Five synthetic drugs that have been approved by the FDA include Tacrine, Rivastigmine, Donepezil, Galantamine, and Memantine for the symptomatic treatment of Alzheimer's. In the search for effective anti-Alzheimer's drugs from a natural source, we discovered marine resources as the origin of the therapeutic and nutritional compound. The methodology involves conducting a comprehensive literature survey. The database search methodology used in this review was the use of keywords, which can be found in the article pertaining to Alzheimer’s disease. The significant articles focused on marine flora phytoconstituents, such as Acetylcholinesterase or butyrylcholinesterase inhibitors, thus prompting a comprehensive review based on pertinent information. The review included descriptions of various studies, revealing that numerous compounds derived from marine sources have demonstrated promising efficacy in the treatment of Alzheimer's disease. Many compounds that originated from marine sources showed good efficacy in treating Alzheimer’s disease. Acetylcholinesterase or butyrylcholinesterase inhibition was the main pharmacological mechanism that was reported for most of the molecules, however, few articles having alternative anti Alzheimer’s mechanisms have also been reported. This article highlights marine compounds derived from marine sources like algae, fungi, and sponges, which can combat Alzheimer's disease.

Neuromuscular Blockade Reversal with Sugammadex Reduces Cardiac Complications and OR Time for Prone Lumbar Spinal Fusion Compared to Neostigmine.

Retrospective cohort study. To evaluate inpatient complication profiles of patients receiving neuromuscular blockade reversal via sugammadex versus neostigmine/glycopyrrolate. Sugammadex is a neuromuscular blockade reversal agent that binds non-depolarizing muscle relaxants. This is a different mechanism from traditional reversal agents such as the combination drug neostigmine (acetylcholinesterase inhibitor)/glycopyrrolate (antimuscarinic agent). Sugammadex has theoretical advantages related to more predictable and rapid reversal, and decreased autonomic side effects. While these agents have been compared in non-spine literature, there is minimal research examining their impact during prone lumbar fusion. All adult patients who underwent a primary one- or two-level posterior lumbar fusion (L4-S1) at a single academic center (2018-2021) were retrospectively identified. Neuromuscular blockade reversal agents (sugammadex or NG), demographics, surgical characteristics, and surgical outcomes were collected through a Structured Query Language search and confirmed by chart review. Bivariate analysis and multivariate linear regression were performed. Alpha was set at P<0.05. In the NG group, more patients had ≥1 inpatient complication (31.2% vs. 19.9%, P=0.012) and cardiac complication (19.1% vs. 11.3%, P=0.040). NG had higher total (0.40±0.66 vs. 0.28±0.62, P=0.046) and cardiac (0.23±0.50 vs. 0.13±0.37, P=0.009) complication rates per person. Operative time was longer amongst patients reversed with NG (182±55.9 vs. 174±55.9, P=0.039). Multivariable linear regression for inpatient complications demonstrated that sugammadex (estimate=-0.124, P=0.045) was negatively predictive of inpatient complications, while Elixhauser (estimate=0.073, P<0.001) was positively predictive. The current results demonstrate that sugammadex may create less risk for cardiac complications, and is likely associated with more rapid reversal and decreased OR time during prone lumbar fusion. However, additional research is needed to further validate these findings, especially amongst patients with cardiac comorbidities.

Centella asiatica Nanoparticles as Potential Acetylcholinesterase Inhibitors for Cognitive Decline Therapy Using the Ellman Method: an In Vitro Study

According to the World Health Organization (2021), cognitive impairment affects 65,6 million elderly people worldwide. Decreased cognitive function in the elderly is caused by neurocognitive changes and inflammation in nerve cells that can interfere with quality of life. Pegagan extract is known to have neuroprotective potential through the active compounds contained in it. An effective drug delivery system is needed so that the active compounds of the drug act as neuroprotective agents through the apoptosis signal inhibition pathway that can cross the blood brain barier (BBB) at adequate concentrations to provide neuroactive effects that support the potential use of this extract as neurotherapy. In this case, pEG-400 was chosen as the drug delivery system. This research was conducted at Universitas Airlangga by covering several stages of testing, namely the GC-MS test to identify active compounds in pegagan extract, tryptamine, γ-sitosterol and β-sitosterol which play a role in improving cognitive function. Synthesis shows that the 1:100 formulation between pegagan extract and pEG-400 produces ideal-sized nanoparticles (5-7 nm), which are optimal for penetrating the BBB. PSA and SEM tests support these results by showing homogeneous particle morphology and consistent chemical composition. High in vitro Ellman's reagent inhibition test with 97.63% effectiveness indicates that the 1:100 formulation is effective as an acetylcholinesterase inhibitor. The 1:1 and 1:100 formulations are very effective in acting as acetylcholinesterase inhibitors. This study shows that the combination of pEG-400 and pegagan extract has great potential as an innovative pharmacological therapy for such cases, but further research is needed to ensure the right dosage and development of research results.

A Comparative UPLC/HRMS Molecular Networking-Enhanced Study on the Phenolic Profiles and Bioactivities of Three Medicinally Significant Species of Onosma (Boraginaceae).

The current work represents a comparative study of the phenolic profiles of three under-explored Onosma (Boraginaceae) species from Greece-Onosma leptantha (OL), Onosma erecta (OE), and Onosma graeca (OG). Although Onosma spp. have ethnopharmacological significance, previous phytochemical studies have focused primarily on roots. Methanolic extracts of the aerial parts were analyzed using qualitative LC-MS enhanced by molecular networking-based dereplication, annotating 94 phenolics categorized into hydroxybenzoic acids (7), hydroxycinnamic acids (24), lignans (14), neolignans (14), stilbenes (4), coumarins (5), and flavonoids (26). OG exhibited the broadest distribution of flavonoid glycosides. OL contained the greatest number of hydroxycinnamic and neolignan derivatives, and OE was notably abundant in lignans. Total phenolic (TPC) and total flavonoid (TFC) contents were quantified, and the antioxidant capacity and enzyme inhibition against cholinesterases, α-amylase, and α-glucosidase were assessed. OL showed a high TPC (69.03 mg GAE/g extract) and strong antioxidant activity, while OG exhibited a high TFC (45.80 mg RE/g extract). All extracts demonstrated stronger AChE inhibition than BChE, with OG showing the highest AChE inhibition (2.35 mg GALAE/g). Additionally, OL was the most active against both α-glucosidase (5.69 mmol ACAE/g) and α-amylase (0.48 mmol ACAE/g). This study improved our understanding of the chemical diversity within these species, providing a more comprehensive insight into their longstanding ethnopharmacological potential.

Exploring the Neuroprotective Effects of Rufinamide in a Streptozotocin-Induced Dementia Model

Due to the complex pathophysiology of AD (Alzheimer’s Disease), there are currently no effective clinical treatments available, except for acetylcholinesterase inhibitors. However, CREB (cyclic AMP-responsive element binding protein) has been identified as the critical factor for the transcription in memory formation. Understanding the effect of potential drugs on the CREB pathway could lead to the development of new therapeutic molecules. Rufinamide has shown promise in improving memory in animal models, and these effects may be associated with modulation of the CREB pathway, however, this has not been previously reported. Thus, the present study aimed to determine the involvement of the CREB pathway in the cognitive improvement effects of rufinamide in STZ (streptozotocin) induced mouse model of dementia. Administration of STZ [3 mg/kg, i.c.v. (intracerebroventricular) bilaterally] significantly impaired cognitive performance in step-down passive avoidance and Morris water maze tests in animals, reduced brain endogenous antioxidant levels (GSH, superoxide dismutase, and catalase), and increased marker of brain oxidative stress [TBARS (thiobarbituric acid reactive substances)] and inflammation [IL-1β (Interleukin-1 beta), IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor alpha) and NF-κB (Nuclear factor kappa B)], along with neurodegeneration. These effects were markedly reversed by rufinamide (50 and 100 mg/kg) when administered to STZ animals. However, the pre-treatment with the CREB inhibitor (666-15) in STZ and rufinamide-administered animals neutralized the beneficial influence of rufinamide. Our data suggest that rufinamide, acting via CREB signaling, reduced oxidative stress and inflammatory markers while elevating anti-oxidant levels. Our study has established that rufinamide may act through CREB signaling in an investigational AD model, which could be crucial for developing new treatments beneficial in progressive neurological disorders.Graphical

Exploring termiticidal properties and GC/MS-based chemical profile of Lantana camara (L.)

India accounts for almost 10 % of the worlds' termite species. Odontotermes horni is one of the most important termites, posing significant threats to agricultural and horticultural ecosystems. The persistent nature of synthetic termiticides necessitates the development of alternative control strategies. The present study investigates the phytochemical composition and potential termiticidal and acetylcholinesterase (AChE) inhibitory properties of Lantana camara (L.) leaf against O. horni. Methanolic, ethyl acetate, and aqueous extracts of L. camara (L.) leaves were used to assess their toxicity. The methanolic extract exhibited the highest potency, with an LC50 of 0.98%, followed by ethyl acetate (1.40 %) and water extract (8.81 %). The per cent mortality recorded at 2.5 % concentration for methanol, ethyl acetate, and aqueous extract was 96.20, 78.75 and 21.25, respectively. By fumigant action, the L. camara (L.) leaf extract at a 5% concentration of methanol, ethyl acetate and aqueous extract resulted in 68.75, 42.50 and 26.25 percent mortality, respectively. The methanolic extract showed the highest AChE inhibition (52.39 %), followed by the ethyl acetate (47.00 %) and the aqueous (43.53 %) extracts after 24 hours of exposure. GC-MS analysis of plant volatiles of the L. camara (L.) revealed 196 compounds, including terpenoids, known for termiticidal activity.

Combination of Probe Electrospray Ionization Mass Spectrometry and Mass Spectrometry Imaging to Analyze Plant Alkaloids in Narcissus tazetta.

Plant alkaloids are used in a variety of medicines, such as anti-cancer drugs and analgesics. Among these plant alkaloids, galanthamine is an Amaryllidaceae type alkaloid with acetylcholinesterase inhibition activity used in the treatment of neurological diseases such as Alzheimer's disease. Although the chemical synthesis of galanthamine has been successfully achieved, Narcissus tazetta is the main source of its production. Research shows that the galanthamine content varies not only with the type of daffodil but also with the stage of development and the part of the plant. Pharmaceutical companies seek plant species with higher galanthamine content to increase pharmaceutical availability. In this study, we were able to rapidly confirm the presence of alkaloids, such as galanthamine, lycorine, and tazettine in the N. tazetta sample using the probe electrospray ionization coupled with quadrupole time-of-flight type mass spectrometry. After confirmation of the components, we then visualized the distribution of the alkaloids by mass spectrometry imaging using the atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometer. In our method, we can provide qualitative data and visualized data immediately.

Novel Schiff Base Sulfonate Derivatives as Carbonic Anhydrase and Acetylcholinesterase Inhibitors: Synthesis, Biological Activity, and Molecular Docking Insights.

Sulfonate derivatives are an essential class of compounds with diverse pharmacological applications. This study presents the synthesis and detailed characterization of six novel Schiff base sulfonate derivatives (L1-L6) through spectroscopic techniques (FTIR and NMR). Their inhibitory potential was evaluated against human carbonic anhydrase isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE), which are crucial therapeutic targets for diseases such as glaucoma, epilepsy, and Alzheimer's disease. The Kivalues for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of, 106.10 ± 14.73-422.80 ± 17.64 nM (THA: 159.61± 8.41 nM), 116.90 ± 24.40-268.00 ± 35.84 nM (AAZ: 439.17 ± 9.30 nM), and 177.00 ± 35.03-435.20 ± 75.98 nM (AAZ: 98.28 ± 1.69 nM), respectively. Molecular docking analyses revealed key interactions within the active sites of the enzymes, including hydrogen bonding with critical residues and π-π stacking interactions. Notably,L3demonstrated superior inhibition against hCA I (Ki: 116.90 ± 24.40 nM) and AChE (Ki: 106.10 ± 14.73 nM), positioning it as a promising lead compound. This comprehensive investigation contributes to the development of isoform-specific inhibitors for therapeutic use and provides valuable insights into their binding mechanisms.

The effect of acetylcholinesterase inhibitor rivastigmine in pentylenetetrazole-induced kindling model of epilepsy in rats.

This study aimed to investigate the role of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor rivastigmine (RIVA) in the pentylenetetrazole (PTZ)- induced kindling model of epilepsy. The current study consists of three steps; 1) Saline or RIVA (0.5, 1, and 2 mg/kg) was administered intraperitoneally (i.p.) 15 min before PTZ (35 mg/kg) during the kindling process and seizure behaviors were observed; 2) Single doses of RIVA (0.25, 0.5, and 1 mg/kg; i.p.) was administered to the electrode implanted kindled rats 15 min before PTZ and electrocorticogram (ECoG) recordings were obtained; 3) Low-dose of RIVA (0.5 mg/kg) was administered to the kindled rats for 14 consecutive days and after 24 h PTZ was administered and ECoG recordings were obtained. In addition, 24 h after the PTZ injection, the hippocampus was extracted and mRNA expression levels of N-methyl D-aspartate receptor subunit 2B (NR2B) and brain-derived neurotrophic factor (BDNF) were measured by qPCR analysis. Only low-dose of RIVA increased resistance against kindling. Single and long-term administration of low-dose RIVA increased the latency to the first myoclonic jerk, decreased the duration of generalized tonic-clonic seizures, and reduced the seizure stage in kindled rats. Long-term low-dose RIVA treatment decreased the mRNA expressions of NR2B and BDNF, which were increased after PTZ kindling. Low-dose of RIVA showed anticonvulsant properties, while high doses did not. RIVA exerts its anticonvulsant effect probably through NMDAR-BDNF pathways. Our results suggest that the use of RIVA may not be harmful and even reduce seizure severity in epileptic patients with convulsions.