Butyrylcholinesterase Enzymes Research Articles

Determination of nutritional composition, enzyme inhibitory activity and antioxidant activity of pretreated, dehydrated <em style="mso-bidi-font-style: normal;">Amaranthus viridis</em> L. Leaves

Amaranthus viridis L., belongs to the family Amaranthaceae is a perennial edible plant, and traditionally used for medicinal treatments in South Asia. Despite the significant uses of the plant, availability of scientific data on plant's biological efficiency is lacking in the scientific domain. There is a higher potential and demand for dehydrated value-added products from the local and international market. Hence, the objective of the research was to determine the impact of pretreatments and dehydration on nutritional composition, phytochemical profile, antioxidant activity, and enzyme inhibitory activity of A.viridis leaves. Magnesium oxide 0.1% (w/v), sodium bicarbonate 0.1% (w/v) and potassium metabisulphite 0.5% (w/v) were selected as the best pretreatment based on the experiments. The pretreated leaves were steam blanched (5 min), followed by dehydration at 60 ± 1°C for 12 hours. Protein (21.90 ± 1.01%db), fat (3.70 ± 0.02%db), fiber (5.90 ± 0.05%db), ash (11.30 ± 0.12%db) and carbohydrate (49.24 ± 0.08%db) were determined. Data was statistically analyzed using one-way analysis of variance (ANOVA) test at a 95% confidence level (p < 0.05). A qualitative phytochemical analysis was conducted. The total phenolic content, 5.89 ± 0.30 mg in Gallic acid equivalents per 1g was determined in pretreated, dehydrated powder. FRAP, DPPH radical scavenging activity and ferrous ion chelating activity of the methanolic extract were 20.22 ± 0.45 mg Trolox equivalents, 1.68 ± 0.07 mg in Trolox equivalents and 3.83 ± 0.06 mg EDTA equivalents per 1g of pretreated dehydrated leaf powder, respectively. Methanolic extract (500 μg/mL) showed inhibitory activity of 25.30 ± 0.60% on 5-lipoxygenase, 30.80 ± 0.50% on alpha-amylase and 25.60 ± 0.40% on alpha-glucosidase. Inhibitory activity was not detected against lipase, acetylcholine esterase and butyrylcholinesterase enzymes. In conclusion, pretreated, dehydrated, A. viridis leaves are recommended as a health beneficial food ingredient.

Organs-specific metabolomics and anticholinesterase activity suggests a trade-off between metabolites for therapeutic advantages of Trillium govanianum Wall. ex D. Don

Trillium govanianum is traditionally used to treat innumerable alignments like sexual disorders, cancer, inflammation etc. Mainly rhizomes of T. govanianum have been explored for phytochemical profiling but comprehensive metabolomics of other parts has not been yet deeply investigated. Thus, current study was aimed for organs-specific (roots, rhizomes, rhizomatous buds, stems, leaves, and fruits) phytochemical profiling of T. govanianum via metabolomics approach. Targeted (steroidal saponins and free sugars) and non-targeted metabolomics were performed by UPLC-PDA/ELSD & UHPLC-Q-TOF-IMS. Among steroidal compounds, 20-hydroxyecdysone, pennogenin-3-O-β-chacotrioside, dioscin were found predominantly in all samples while diosgenin was identified only in rhizomes. Further, four free sugars viz. 2-deoxyribose (116.24 ± 1.26 mg/g: leaves), fructose (454.76 ± 12.14 mg/g: rhizomes), glucose (243.21 ± 7.53 mg/g: fruits), and galactose (69.06 ± 2.14 mg/g: fruits) were found significant in respective parts of T. govanianum. Elemental analysis of targeted samples was determined by atomic absorption spectrophotometer. Heavy metals (Cd, Hg, Pd, As) were absent while micro- (Mn, Na, Zn, Cu) and macro- (Ca, Fe, Mg, K) elements were found in all samples. Furthermore, UHPLC-Q-TOF-IMS had identified 103 metabolites based on their mass fragmentation patterns and 839 were tentatively predicted using METLIN database. The multivariate statistical analysis showed organs specific clustering and variance of metabolites. Apart from this, extracts were evaluated for in vitro anticholinesterase activity, and found potentials inhibitors with IC50 values 2.02 ± 0.15 to 27.65 ± 0.89 mg/mL and 3.58 ± 0.12 to 16.81 ± 2.48 mg/mL of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme, respectively. Thus, comprehensive metabolomics and anti-cholinesterase activity of different parts of T. govanianum would lay the foundation for improving medicinal importance and health benefits of T. govanianum.

Physiochemical characterization of Glycyrrhiza mediated bioengineered palladium nanoparticles (PdNPs), their anti-proliferative and other biomedical applications

The study used licorice root leaf extract to synthesize palladium nanoparticles (PdNPs) that demonstrate long-term stability, lower toxicity, and enhanced penetration into specific target cells. The optimal conditions (temperature, pH, and time) were maintained to synthesize regular, spherical, and homogenous nanoparticles. The PdNPs were characterized by Energy dispersive X-ray spectroscopy, UV–Visible spectroscopy, High-resolution Transmission electron microscope, X-ray diffraction, Particle-Size Distribution, Fourier Transform Infrared Spectroscopy, X-ray photoelectron spectroscopy, and Zeta potential analysis. The biosynthetic PdNPs used ABTS and DPPH assay to demonstrate strong antioxidant potential with maximal inhibition. PdNPs hindered the growth of Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa with zone of inhibition that was 20–25 ± 0.22 mm. PdNPs showed anti-Alzheimer activity by suppression of acetylcholinesterase and butyryl cholinesterase enzymes. Furthermore, the minimum anti-proliferative concentration of PdNPs was detected against MCF-7 and HCT-116 which was 44.4 at 6.58 µg/mL, respectively. Thus, PdNPs have proved to be an effective therapeutic agent for drug delivery and other biomedical applications in the pharmaceutical industry.

Centrosymmetric Homo- and Heteroleptic Core Paddle-wheel Copper(II) Carboxylates; Syntheses, Crystal Structures, Antioxidant, Anticancer and Enzyme Inhibition Activity

Synthesis and characterization of homo- (C5H7N2)2[Cu2(3,5-F2C6H3CH2COO)6] (1) and heteroleptic [Cu2(3,5-F2C6H3CH2COO)4(2-CH3Py)2] (2) core paddle-wheel copper(II) carboxylates is reported in the present work. The characterization was made by spectroscopic techniques, elemental and single crystal XRD analyses. The single crystal XRD analysis revealed a rare homoleptic anionic copper(II) carboxylate complex (1) consisting 2-aminopyridinium counter cations and a neutral heteroleptic copper(II) carboxylate complex (2) consisting 2-methyl pyridine as a co-ligand. The copper ions adopted a distorted square pyramidal geometry in both the paddle-wheel dimeric complexes. To evaluate the biological potency of the synthesized complexes, in vitro antioxidant, enzymes inhibition and anticancer activities were performed. The synthesized complexes have shown overall better biological activity compared to the ligand acid. Complex 2 was the most potent DPPH (IC50 =180.96 ± 9.04 µg/mL) and •OH (IC50 = 189.51 ± 9.33 µg/mL) radicals scavenger, α-amylase (IC50 = 441.86 µg/mL) and acetylcholinesterase (IC50 = 88.62 µg/mL) inhibitor. Furthermore, complex 2 activity against malignant glioma U-87 cell line (IC50 = 21.95 µg/mL) was also highest among the tested compounds. However, complex 1 with an IC50 value of 51.83 µg/mL has shown somewhat better inhibition of the butyrylcholinesterase enzyme compared to the complex 2 (IC50 = 56.36 µg/mL).

Neuroprotective properties of UV-C treated Bacopa floribunda leaves: in vitro and in vivo studies

This study investigated the effect of UV-C irradiation on antioxidant, cholinergic and neuroprotective properties of Bacopa floribunda leaves in scopolamine-induced rats. In vitro study was done by the determination of phenolics, flavonoid, total antioxidant capacity, 2, 2-diphenyl-1-picrylhydrazyl scavenging activity, inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Loss of memory was induced in Wistar rats pre-treated with extracts of Bacopa floribunda using scopolamine (2 mg/kg) administered intraperitoneally. Behavioural studies using elevated plus maze (EPM) and biochemical analysis on the were carried out. Exposure to UV-C radiation increased the phenolics, flavonoid, antioxidant and inhibitory properties against AChE and BChE of the Bacopa floribunda leaves. The administration of scopolamine caused significant increase in the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, but decrease in the activities of antioxidant enzymes and enhanced generation of malondialdehyde and nitric oxide in vivo. The loss of memory and Biochemical analysis in scopolamine-induced rats was ameliorated by treatment with UV-C treated Bacopa floribunda (TBF) extracts. Treatment with TBF improved memory retention and ameliorated oxidative damage in hippocampus of scopolamine treated rats.

Synthesis, characterization, crystal structure, biological activities, and molecular docking study of the (NHC)Pd(II)(Morp) (NHC: N-heterocyclic carbene, Morp: Morpholine) complexes

In this paper, a new palladium-based (NHC)Pd(II)(Morp) complexes (NHC: N-heterocyclic carbene, Morp: morpholine) were prepared. The NHC ligand in these complexes bears the 2-chloro-4-fluorobenzyl group. All complexes were fully characterized by 1H, 13C NMR, FTIR spectroscopic and elemental analysis methods. The crystal structure of complex 1f has been determined by using single-crystal X-ray diffraction. Furthermore, all complexes were investigated for their ability to inhibit enzymes. All complexes exhibited highly potent inhibition effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes (Ki values are in the range of 97.84 ± 8.97 to 132.28 ± 11.63 µM and 18.24 ± 2.08 to 39.08 ± 5.28 µM for AChE and BChE, respectively). Designing of reported complexes is impacted by molecular docking study, because with molecular docking study, it will lead to future researches by illuminating the interaction mechanism of complexes 1a, 1b, 1c and 1f with potential activity against target AChE and BChE enzymes at molecuar level.

Interaction of exogenous acetylcholinesterase and butyrylcholinesterase with amyloid-β plaques in human brain tissue

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are associated with amyloid-β (Aβ) plaques and exhibit altered biochemical properties in human Alzheimer's disease (AD), as well as in the transgenic 5XFAD mouse model of AD amyloidosis. In the brains of the 5XFAD mouse model devoid of BChE enzyme (5XFAD/BChE-KO), incubation of tissue sections with exogenous BChE purified from human plasma (pl-BChE) leads to its association with Aβ plaques and its biochemical properties are comparable to those reported for endogenous BChE associated with plaques in both human AD and in 5XFAD mouse brain tissue. We sought to determine whether these observations in 5XFAD/BChE-KO mice also apply to human brain tissues. To do so, endogenous ChE activity in human AD brain tissue sections was quenched with 50 % aqueous acetonitrile (MeCNaq) leaving the tissue suitable for further studies. Quenched sections were then incubated with recombinant AChE (r-AChE) or pl-BChE and stained for each enzymes' activity. Exogenous r-AChE or pl-BChE became associated with Aβ plaques, and when bound, had properties that were comparable to the endogenous ChE enzymes associated with plaques in AD brain tissues without acetonitrile treatment. These findings in human AD brain tissue extend previous observations in the 5XFAD/BChE-KO mouse model and demonstrate that exogenously applied r-AChE and pl-BChE have high affinity for Aβ plaques in human brain tissues. This association alters the biochemical properties of these enzymes, most likely due a conformational change. If incorporation of AChE and BChE in Aβ plaques facilitates AD pathogenesis, blocking this association could lead to disease-modifying approaches to AD. This work provides a method to study the mechanism of AChE and BChE interaction with Aβ plaque pathology in post-mortem human brain tissue.

LC/MS-Based Metabolomics Reveals Chemical Variations of Two Broccoli Varieties in Relation to Their Anticholinesterase Activity: In vitro and In silico Studies.

Broccoli is commonly consumed as food and as medicine. However, comprehensive metabolic profiling of two broccoli varieties, Romanesco broccoli (RB) and purple broccoli (PB), in relation to their anticholinergic activity has not been fully disclosed. A total of 110 compounds were tentatively identified using UPLC-Q-TOF-MS metabolomics. Distinctively different metabolomic profiles of the two varieties were revealed by principal component analysis (PCA). Furthermore, by volcano diagram analysis, it was found that PB had a significantly higher content of phenolic acids, flavonoids, and glucosinolates, indicating the different beneficial health potentials of PB that demonstrated higher antioxidant and anticholinergic activities. Moreover, Pearson's correlation analysis revealed 18 metabolites, mainly phenolic and sulfur compounds, as the main bioactive. The binding affinity of these biomarkers to the active sites of acetyl- and butyryl-cholinesterase enzymes was further validated using molecular docking studies. Results emphasize the broccoli significance as a functional food and nutraceutical source and highlight its beneficial effects against Alzheimer's disease.

The role of mivacurium in contemporary anesthesiology: a narrative review

Background: Mivacurium is the shortest-acting non-depolarizing neuromuscular blocking agent (NMBA) with a rapid onset of action that is mainly used for short procedures. Despite the fact that mivacurium has a very favorable average 6-minute recovery index after its infusion in comparison to the approximately 15–30 minutes for atracurium, mivacurium is still not really popular among practicing anesthesiologists. Many new studies showing the potential further benefits of implementing mivacurium into daily practice are still being published. Aim of the Study: This study aimed to focus on spreading the common knowledge about the detailed pharmacokinetic and pharmacodynamic properties of mivacurium as a medication that has yet to be used widely by practicing anesthesiologists. Material and methods: The literature review was conducted using the common sources of original articles such as PubMed and Google Scholar from 1975 to September 2022. Results: Based on the literature review, we observed that Mivacurium at a dosage of 6μg produces a lower impact on hemodynamics, shorter intubation and extubation times, faster postoperative recovery, absence of the accumulation of neuromuscular blockade, higher safety, and no significant increase in allergic related adverse events in comparison with other NMBAs.Conclusions: Mivacurium is a muscle relaxant medication that is particularly suited for short-lasting surgical procedures. However, it is important to remember that existing mutations in the butyrylcholinesterase enzyme (BChE) may prolong the effect of the neuromuscular blockade due to significantly reducing plasma cholinesterase activity. Therefore, it is advised to stay cautious during its use as more research needs to be done to be able to thoroughly assess the potential advantages and disadvantages of mivacurium introduction in particular patients

Sulfonamide Derivatives: Recent Compounds with Potent Anti-alzheimer's Disease Activity.

Facile synthetic procedures and broad spectrum of biological activities are special attributes of sulfonamides. Sulfonamide derivatives have demonstrated potential as a class of compounds for the treatment of Alzheimer's disease (AD). Recent sulfonamide derivatives have been reported as prospective anti-AD agents, with a focus on analogues that significantly inhibit the function of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and exhibit remarkable antioxidant and anti-inflammatory properties, all of which are critical for the treatment of AD. Sulfonamide- mediated activation of nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of the endogenous antioxidant response, has also been suggested as a potential therapeutic approach in AD. Additionally, it has been discovered that a number of sulfonamide derivatives show selectivity for the β- and γ-secretase enzymes and a significant reduction of amyloid B (Aβ) aggregation, which have been implicated in AD. The comparative molecular docking of benzenesulfonamide and donepezil, an AD reference drug showed comparable anti-AD activities. These suggest that sulfonamide derivatives may represent a new class of drugs for the treatment of AD. Thus, the current review will focus on recent studies on the chemical synthesis and evaluation of the anti-AD properties, molecular docking, pharmacological profile, and structure-activity relationship (SAR) of sulfonamide derivatives, as well as their potential anti-AD mechanisms of action. This paper offers a thorough assessment of the state of the art in this field of study and emphasizes the potential of sulfonamide derivatives synthesized during the 2012-2023 period as a new class of compounds for the treatment of AD.

Indolyl imine compounds as multi-target agents; synthesis, antidiabetic, anticholinesterase, antioxidant activities and molecular modeling

A new range of indolyl imine system 3d-l has been successfully prepared from 4,6-dimethoxy-2,3-diphenyl-indole-7-carbaldehyde 2a and 4,6-dimethoxy-3-aryl-indole-7-carbaldehyde 2b-cvia Schiff base reaction. The structure of targeted compounds was confirmed by 1H and 13C NMR, FT-IR, mass spectrometry and single crystal X-ray diffraction techniques. The indolyl imine derivatives were also subjected to in vitro antidiabetic activities employing α-glucosidase and α-amylase enzymes. In terms of antidiabetic investigation, the α-glucosidase enzyme was found to be potential target due to the comparable inhibition concentrations with the standard acarbose and the compound 3e exhibited better potency than the standard. The anticholinesterase potency of the compounds was investigated towards the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The compounds displayed moderate efficiency against the BChE enzyme with the best inhibition concentration of 30.48 μM by the compound 3h. The antioxidant properties of final compounds were determined by DPPH radical scavenging, ABTS Cation Radical Decolarization and CUPRAC Cupric Reducing Antioxidant Capacity assay methods. The ABTS cation scavenging assay provided the best responses for the compounds and the candidates 3k and 3l were determined as promising targets for the antioxidant activity. Plausible binding mode and interaction of ligands with the selected enzyme have been studied by molecular docking, supporting the experimental results. In silico ADME showed high drug likeness of the synthesized compounds.

Cholinesterase Inhibitory Compounds from Peltophorum Pterocarpum Flowers

AbstractNeurodegenerative disorders (NDs), such as Alzheimer’s and Parkinson disease, affect millions of people worldwide. Natural cholinesterase inhibitors are an important class of lead drugs that have gained much interest for the management of NDs in recent time. They continue to provide promising alternatives to synthetic ones because of their more superior drug-like properties. The aerial part of Peltophorum petrocarpum is popularly used in the African ethnomedicine as a remedy for memory loss. The leaves have been explored for their cholinesterase compounds, while the flowers are yet to be investigated. Therefore, the study evaluated the flower extract for its cholinesterase inhibitory compounds. An activity-guided fractionation of the extract led to the isolation and characterization of two cholinesterase inhibitory compounds, namely: bergenin (1) and a newly described coumarin derivative, 3,4,5,5a-tetrahydroxy-2-(hydroxymethyl)-3-(4-hydroxyphenyl)-9-methoxy-3,5,5,5a-tetrahydro-2 H-oxepino[3,2-c]chromen-6-(11bH)one, named peltophorin (2). The compounds were isolated on repeated silica gel and Sephadex LH-20 column chromatography of the ethyl acetate fraction. Their structures were elucidated by comparison of the mass spectrometry (ESI-MS) and the nuclear magnetic resonance spectroscopy (1D- and 2D-NMR) data to literature reports. Both compounds demonstrated in vitro inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes involved in neurodegeneration. The identified compounds exhibited a comparable AChE inhibitory activity (IC50 = 90 µM), which is lower than eserine, the positive control at IC50 of 12.4 ± 0.4 and 21.0 ± 1.0 µM against AChE and BuChE enzymes, respectively. Bergenin (1) notably demonstrated better BuChE inhibitory activity, with an IC50 of 57.1 ± 8.0 µM compared to peltophorin (2). In conclusion, this study has shown that the flowers of P. pterocarpum contain cholinesterase inhibitors such as bergenin and the newly described peltophorin, thus adding to the repository of natural coumarins with anti-cholinesterase activity.

New benzimidazole based Schiff bases as potent anti-alzheimer agents: Synthesis, bio-evaluation and molecular docking study

In search of potent anti-Alzheimer agent benzimidazole based Schiff base derivatives (1–18) were synthesized and evaluated as dual inhibitor for acetylcholinesterase and butyrylcholinesterase enzymes. All analogs among the series except analog 1 and 16 showed a variable degree of inhibitory activity with IC50 value ranging between 0.10 ± 0.01 to 12.40 ± 0.30 µM for acetylcholinesterase and 0.20 ± 0.01 to 11.10 ± 0.30 µM for butyrylcholinesterase. The most potent analog found among the series was analog 8 having IC50 value 0.10 ± 0.01 and 0.20 ± 0.01 µM for both acetylcholinesterase and butyrylcholinesterase inhibition respectively. The structures of all synthesized analogs were confirmed through NMR and HR-EIMS. Structure activity relationship (SAR) has been established for all newly synthesized derivatives. To understand the binding interaction of most active derivatives with enzyme active site, molecular docking study were performed. The toxicity and mutagenicity of compound 8 was predicted using in silico software, namely Derek Nexus® (version 6.3). Various toxicity endpoints, including chromosomal damage, skin sensitization, hepatotoxicity were predicted. The degradation profile of compound 8 was predicted in silico by Zeneth software (version 9.0.1) resulting in a probability of the formation of seven potential degradation products.

Synthesis and in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes activity of aldehyde and Schiff base substituted cobalt (II), copper (II), and zinc (II) phthalocyanines

In this work, a series of aldehyde‐substituted phthalocyanine compounds (1, 3, and 5) were prepared by the cyclotetramerization of the 4‐(5‐(diethylamino)‐2‐formylphenoxy) phthalonitrile (a) and the corresponding metal salts. Schiff base‐substituted phthalocyanines (2, 4, and 6) were derived from an aldehyde‐substituted phthalocyanine (1, 3, and 5) via the reaction of aldehyde‐substituted phthalocyanines with an amine reagent. The compounds that were obtained were characterized using FT‐IR, 1H {13C} NMR, UV–Vis, and MS spectra (a and 1–6). The inhibitory qualities of synthesized aldehyde and Schiff base‐substituted complexes against the enzymes butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) were assessed. The majority of phthalocyanines exhibited strong enzyme‐inhibiting properties. Out of the six produced phthalocyanines, 3 and 4 displayed the most intriguing profiles as submicromolar selective AChE inhibitors (IC50 = 0.060 μM), whereas 1 demonstrated the most potent BChE inhibitor (IC50 = 0.024 μM). The aggregation studies of CoPcs, CuPcs, and ZnPcs (1–6) were also carried out in this work.

Potential acetylcholinesterase inhibitors to treat Alzheimer's disease.

Alzheimer's disease (AD) is identified by neuropathological symptoms, and there is now no effective treatment for the condition. A lack of the brain neurotransmitter acetylcholine has been related to the etiology of Alzheimer's disease. Acetylcholinesterase is an enzyme that breaks down acetylcholine to an inactive form and causes the death of cholinergic neurons. Conventional treatments were used but had less effectiveness. Therefore, there is a crucial need to identify alternative compounds with potential anti-cholinesterase agents and minimal undesirable effects. Fluoroquinolones and benzimidazole-benzothiazole derivatives offer antimicrobial, anti-inflammatory, anti-oxidant, anti-diabetic, and anti-Alzheimer activities. To enhance the chemical portfolio of cholinesterase inhibitors, a variety of fluoroquinolones and benzimidazole-benzothiazole compounds were evaluated against acetylcholinesterase (AChE) butyrylcholinesterase (BChE) enzymes. For this purpose, molecular docking and adsorption, distribution, metabolism, excretion, and toxicology ADMET models were used for in-silico studies for both AChE and BChE enzymes to investigate possible binding mechanisms and drug-likeness of the compounds. The inhibitory effect of docked heterocyclic compounds was also verified in vitro against AChE and BChE enzymes. Fluoroquinolones (Z, Z3, Z4, Z6, Z8, Z12, Z15, and Z9) and benzimidazole-benzothiazole compounds (TBIS-16, TBAF-1 to 9) passed through the AChE inhibition assay and their IC50 values were calculated. The compound 1-ethyl-6-fluoro-7-(4-(2-(4-nitrophenylamino)-2-oxoethyl)piperazin-1-yl) -4-oxo-1,4 di-hydroquinoline-3-carboxylic acid and 2-((1H-benzo[d]imidazol-2-yl)methyl)-N'-(3-bromobenzyl)-4-hydroxy-2H-thiochromene-3-carbohydrazide 1,1-dioxide (Z-9 and TBAF-6) showed the lowest IC50 values against AChE/BChE (0.37±0.02/2.93±0.03 µM and 0.638±0.001/1.31±0.01 µM, respectively) than the standard drug, donepezil (3.9±0.01/4.9±0.05 µM). During the in-vivo investigation, behavioral trials were performed to analyze the neuroprotective impact of Z-9 and TBAF-6 compounds on AD mouse models. The groups treated with Z-9 and TBAF-6 compounds had better cognitive behavior than the standard drug. This study found that Z-9 (Fluoroquinolones) and TBAF-6 (benzimidazole-benzothiazole) compounds improve behavioral and biochemical parameters, thus treating neurodegenerative disorders effectively.

Qualitative chemical compounds analysis and in vitro estimation of antiproliferative, antidiabetic and anti-Alzheimer’s disease effects of Ononis natrix (L.) family Fabaceae

The O. natrix belongs to the family Fabaceae and is distributed in Jordan. Different species of the family Fabaceae contain chemical compounds that may have potential antiproliferative, antidiabetic, and anti-Alzheimer’s disease. High-performance liquid chromatography (HPLC) was applied to analyse the phenolic compounds found in O. natrix methanolic extract. Using the MTT assay, the antiproliferative action was studied. The enzymes α-glucosidase and butyrylcholinesterase inhibition assays were used to study the antidiabetic and anti-Alzheimer’s disease actions, respectively, of methanolic extract of O. natrix. Eleven phenolics and seven flavonoids were identified in the methanolic extract of O. natrix by HPLC. The highest phenolics and flavonoids were gallic acid (1.25 mg/100 g dry weight) and rutin (1.44 mg/100 g dry weight), respectively. The most cancer cell lines influenced by the extract of O. natrix were PC-3 (IC50 = 55 ± 2 µg/mL) and HepG-2 (IC50 = 68 ± 2 µg/mL) compared to positive control cisplatin. However, the cancer cell lines CaCo-2, MCF-7, and HeLa showed IC50 values of 109 ± 2 µg/mL, 123 ± 2 µg/mL, and 79 ± 1 µg/mL, respectively, related to cisplatin. The O. natrix extract inhibited the α-glucosidase enzyme and butyrylcholinesterase enzyme by 84% and 86%, respectively compared to positive controls acarbose and rivastigmine. The O. natrix may possess antiproliferative effects against prostate cancer and hepatocellular carcinoma. It also may have antidiabetic and anti-Alzheimer’s disease effects.

Synthesis, in vitro biological evaluation and in silico molecular docking study of hydroxy‑quinoline based sulfonohydrazide derivatives as potential acetylcholinesterase and butyrylcholinesterase inhibitors

A series of hydroxy‑quinoline-based sulfonohydrazide derivatives (1–16) were synthesized and their structures were elucidated by using various spectroscopic tools including 1HNMR, 13CNMR and HREI-MS and evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All synthesized derivatives showed the varied range of AChE and BuChE activities having IC50 values ranging from 0.20 ± 0.01 to 11.60 ± 0.20 µM (against AChE) and 0.80 ± 0.05 to 22.70 ± 0.30 µM (against BuChE) as compared to standard drug Donepezil (IC50 = 2.16 ± 0.12 µM & 4.5 ± 0.11 µM, respectively). Among the series, compounds 1, 8, and 10 were identified to be most potent, even more, active than standard drug having IC50 values of 0.40 ± 0.05, 0.20 ± 0.01, 0.70 ± 0.05 µM (against AChE) and 0.80 ± 0.05, 0.80 ± 0.05, 2.10 ± 0.10 µM (against BuChE) respectively. Based on the substitution pattern around the aryl ring, structure-activity relationship (SAR) analysis was conducted for all synthesized derivatives. Additionally, the molecular docking method was created to investigate the mechanism of interactions between the scaffolds that are most active and the active sites of specific AChE and BuChE enzymes.

An In Silico and In Vitro Assessment of the Neurotoxicity of Mefloquine.

Mefloquine (MQ) is a quinoline-based anti-malarial drug used for chemoprophylaxis or as a treatment in combination with artesunate. Although MQ has clear anti-Plasmodium falciparum properties, it can induce neurotoxicity and undesired neuropsychiatric side effects in humans. Hence, this study aimed to characterize the neurotoxicity of MQ using human neuroblastoma SH-SY5Y cells. The effects of MQ on neuronal toxicity and cell viability were investigated over a concentration range of 1-100 µM using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. The influence of MQ on cellular bioenergetics was examined by measuring cellular ATP levels and from the induction of reactive oxygen species (ROS). An in silico approach was used to assess the potential neurotoxicity of MQ mediated via binding to the active sites of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) and then experimentally validated via in vitro enzymatic assays. MQ was cytotoxic to neuronal cells in a concentration and exposure duration dependent manner and induced a significant reduction in viability at concentrations of ≥25 µM after a 24 h exposure. MQ adversely impacted cellular bioenergetics and significantly depleted ATP production at concentrations of ≥1 µM after 24 h. MQ-induced cellular ROS production, which was correlated with the induction of apoptosis, as revealed by flow cytometry. In silico studies suggested that MQ was a dual cholinesterase inhibitor and one with remarkably potent binding to BuChE. Modelling data were supported by in vitro studies which showed that MQ inhibited both human AChE and BuChE enzymes. In summary, MQ is an antimalarial drug that may induce neurotoxicity by impacting cellular bioenergetics and perturbing the activity of cholinesterases at exposure concentrations relevant to human dosage.

Exploring the potential of Cytisus purgans as a source of bioactive molecules: In vitro pharmacological evaluation

IntroductionCytisus purgans is an uncommon species found in Algeria (Aures, Mahdids and Lella Khadidja). In the current study, we present, to the best of our knowledge, the first detailed chemical profile of its extracts and collect various pieces of evidence that underscore their therapeutic potential. MethodsThe ethyl acetate extract (EAE) of C. purgans was purified using different chromatographic methods. The bioactive compounds obtained were analysed by NMR and mass spectroscopy to identify their structures. The therapeutic potential of the extracts was investigated using several in vitro assays. Results and discussionThe developed spectral analysis techniques enabled the structural elucidation of seven compounds. The analysis identified four isoflavones, including daidzein, genistein, isoprunetin and biochanin A. Additionally, one flavone, chrysin and one flavonol, quercetin, were positively identified. Notably, the phytosterol daucosterol was also isolated and characterised. The studied extracts were found to be rich in polyphenols and flavonoids. The EAE had the highest polyphenolic (163.85 ± 3.82 mg GAE/g dry extract) and flavonoid content (180.84 ± 3.68 mg QE/g dry extract). The extracts showed potent anti-oxidant activity, as demonstrated by DPPH 50 % inhibitory concentration (EAE: IC50 = 26.66 µg/mL, BuE: IC50 = 30.91 µg/mL), ferric reducing anti-oxidant power IC50 (EAE: IC50 = 6.37 ± 0.27 µg/mL, BuE: IC50 = 13.02 ± 0.1 µg/mL) and total anti-oxidant capacity values (EAE 106.57 ± 5.81 AAE/g dry extract, BuE 105.46 ± 8.64 AAE/g dry extract). This anti-oxidant activity contributed significantly to effective sun protection (EAE sun protection factor (SPF) = 87.84, BuE SPF = 31.67). Additionally, the extracts inhibited acetylcholinesterase (EAE IC50 = 24.40 ± 2.84 µg/mL, BuE IC50 = 68.07 ± 02.26 µg/mL) and butyrylcholinesterase enzymes (EAE IC50 = 36.39 ± 0.75 µg/mL, BuE IC50 = 66.19 ± 01.25 µg/mL) the most and significantly inhibited urease (EAE IC50 = 77.82 ± 4.59 µg/mL, BuE IC50 = 127.05 ± 2.87 µg/mL). ConclusionConsidering the findings, C. purgans emerges as a promising reservoir of bioactive compounds that have the potential to contribute to the development of treatments for specific diseases. The identification of these compounds and their therapeutic potential provides valuable insights into their potential use in drug development.

Phytoconstituents, antioxidant, and cholinesterase inhibitory activities of the leaves and stem extracts of Artocarpus sericicarpus

The study aimed to investigate the antioxidant and cholinesterase inhibitory activities of the leaves and stems of Artocarpus sericicarpus and to analyse the phenolic compounds in the extracts. The modified Ellman’s method was used to determine the cholinesterase inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The antioxidant properties were evaluated using DPPH and ABTS methods. The total phenolic content (TPC) was measured by spectrometric assay, and compound identification was carried out by LC-MS/MS analysis. The results showed that the leaf and stem extracts of A. sericicarpus exerted significant inhibitory effects against AChE and BChE, as well as antioxidant activities. The stem ethanolic extract exhibited the highest potency against AChE and BChE with IC50 values of 5.81 and 11.46 µg/mL, respectively. The leaf and stem ethanolic extracts gave higher antioxidant activities and TPC compared to the water-based extracts. The LC-MS/MS analysis indicated the presence of phenolic compounds, such as flavones, flavonols, flavanones, prenylated chalcones, and xanthones in the extracts.