Acetylcholinesterase Enzyme Research Articles

Ondansetron attenuates cisplatin-induced behavioral and cognitive impairment through downregulation of NOD-like receptor inflammasome pathway

Cisplatin is an effective and commonly used chemotherapeutic drug; however, its use is accompanied by several adverse effects, including chemobrain. Ondansetron is a 5-HT3 antagonist, commonly used in prophylactic against chemotherapy-induced nausea and vomiting. Moreover, it has been identified as a novel neuroprotective agent in different animal models. However, its protective role against chemotherapy-induced chemobrain has not been investigated. The current study was the first study that explored the potential neuroprotective effect of ondansetron against cisplatin-induced chemobrain in rats. Cisplatin (5 mg/Kg) was injected intraperitoneally, once weekly, for 4 weeks with the daily administration of ondansetron (0.5 and 1 mg/Kg). Compared to the cisplatin-treated group, ondansetron administration showed a significant decrease in the latency time and a significant increase in ambulation, rearing, and grooming frequency in the open field test (OFT). Moreover, a significant improvement in the latency time in the rotarod and passive avoidance tests, following ondansetron administration. In addition, ondansetron treatment increased the percentage of alternation in the Y-maze test. Also, ondansetron showed a remarkable enhancement in the biochemical parameters in the hippocampus. It increased the acetylcholine (Ach) level and decreased the level of the acetylcholine esterase enzyme (AchE). Ondansetron significantly decreased interleukin-1β (Il-1β), tumor necrosis factor-alpha (TNF-α), toll-like receptor-4 (TLR-4), NOD-like receptor-3 (NLRP3) inflammasome as well as caspase-1 and caspase-3 levels. Furthermore, ondansetron significantly decreased the levels of copper transporter-1(CTR1) expression in the hippocampus. Collectively, these findings suggest that ondansetron may exhibit a neuroprotective and therapeutic activity against cisplatin-induced chemobrain.

Acetylcholinesterase enzyme among cancer patients a potential diagnostic and prognostic indicator a multicenter case–control study

Acetylcholinesterase enzyme (AChE) activity is impaired by a variety of inhibitors including organophosphorus pesticides, leading to the accumulation of acetylcholine. In this study, we aimed to determine the association between cancer and the blood level of the (AChE). This is a multicenter hospital-based case–control study conducted in the Radiation and Isotopes Center Khartoum, and Institute of Nuclear Medicine and Molecular Biology and Oncology Gezira. One hundred and fifty participants, half of them cancer patients and half cancer free were recruited. All participants were screened for demographic, environmental, occupational, and clinical characteristics. Blood for the (AChE) activity test was drawn from participants in the two groups. The mean age of the participants was 40.6 ± 14.8 years. Geographical distribution showed the Central Region of Sudan had the highest rate of cancer, followed by North State, Khartoum State, West State, and East State. The most common tumor subtype was breast cancer, followed by leukemia, colon, esophageal, and prostate cancer. Inferential analysis revealed significantly impaired (AChE) activity among cancer patients compared to controls (53.4 ± 20.3% vs. 93.8 ± 8.8, p-value 0.001). There was a significant statistical association between impaired (AChE) activity and cancer. (AChE) activity might be applied in the future as a diagnostic biomarker and therapeutic target. Further large sample and molecular studies are recommended.

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.

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.

Screening of Oxystelma esculentum R.BR extracts for Acetylcholinesterase Inhibitory Activity

The loss of memory is considered to be the result of deficiency of nerve transmitter acetylcholine. The acetyl cholinesterase responsible for the breakdown of neurotransmitter acetylcholine leading to decline in cognitive function. The Currently available AchE inhibitors are reported to be ineffective in treating mild cognitive impairments because of side effects. Therefore, current work focused on acetylcholinesterase enzyme. A wide variety of medicinal plants are available as acetylcholinesterase inhibitors as they are rich source of bioactive compounds like poly phenolic compounds. Owing to these background research, various extracts of Oxystelma esculentum were screened for acetylcholinesterase inhibiting assay. The present study revealed that ethanol extract of oxystelmaesculentum showed effective AchE inhibition activity compared with other extracts. However further studies on investigation of active principles from the ethanol extract of Oxystelma esculentum as inhibitors of AchE are in process in our laboratory.

Alcohol and Caffeine Co-Administration Increased Acetylcholinesterase Activity and Inflammatory Cytokines in Sleep-Deprived Rats: Implications for Cognitive Decline and Depressive-Like Manifestations.

Sleep deprivation is a major health problem in modern society; it has been worsened by alcohol and caffeine intake to stay awake and improve bodily activities, an experience common among night-shift workers. For the present study, 50 adult male Wistar rats weighing between 150 g and 200 g were randomly selected and divided into 5 groups of 10 rats each (n = 10). Group 1 was the control group; group 2 was the group of sleep-deprived (SD) rats; group 3 was composed SD rats submitted to the administration of 20% alcohol; group 4 comprised SD rats submitted to the administration of 200 mg/kg of caffeine; and Group 5 was composed of SD rats who underwent the co-administration of 20% alcohol and 200 mg/kg of caffeine. At the end of 28 days, the animals were euthanized, and blood samples were collected for biochemical analysis. Memory, anxiety, social behavior and locomotive activity were assessed using the Y-maze, the elevated plus maze, the hole-board and three-chambered social approach tests, and the open field test. The plasma levels of the acetylcholinesterase (AChE) enzyme and inflammatory cytokines (interleukin 6 [IL-6], interleukin 10 [IL-10], and tumor necrosis factor beta, [TNF-β]) were also measured. Data was expressed as mean ± standard error of the mean [SEM] values, and the data were analyzed through analysis of variance (ANOVA) followed by the Tukey post hoc test, with significance set at p < 0.05 . The results revealed that sleep deprivation, and the co-administration of alcohol and caffeine impair memory in rats. Sleep deprivation also caused a significant increase in anxiety and anxiety-related behavior, with decreased social interaction, in rats. Locomotive activity was improved in SD rats, especially in those to which alcohol was administered. Sleep deprivation significantly reduced acetylcholinesterase activity among SD rats and those to which alcohol was administered when compared with the controls. The plasma levels of IL-6, IL-10 and TNF-β were significantly increased in SD rats when compared with the controls. The administration of alcohol and caffeine separately, as well as their co-administration, significantly increased cytokine levels in rats.

Synthesis and in vitro carbonic anhydrase and acetylcholinesterase inhibitory activities of novel hydrazide–hydrazone compounds containing 1,2,4-triazole ring

In this work, 1,2,4-triazole derived hydrazide–hydrazones were synthesized with a five-step synthesis pathway. The novel derivatives were characterized by various analytical methods. Acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) inhibitory qualifications of these thirteen original compounds (4, 5a–l) were also determined. The overall biological activity results were very interesting. The reported compounds were found to be very effective inhibitors of hCA I, hCA II, and AChE enzymes with IC50 values in the range of 17.33−77.00 nM for hCA I (Acetazolamide IC50: 62.80 nM), 13.07−46.20 nM for hCA II (Acetazolamide IC50: 57.75 nM) and 4.91−36.47 nM for AChE (Tacrine IC50: 28.88 nM). Within the new compounds, 5i displayed the best hCA I, hCA II and AChE inhibitory activities with IC50 values of 17.33 nM, 13.07 nM, and 4.91 nM, respectively.

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.

In silico and in vitro biopesticidal activity of Melia dubia (Cav.) plant leaves extract phytocompounds against selected enzymes, proteins, cell lines and Callosobruchus maculatus (Fab.)

Most synthetic pesticides have negative impacts on both human health and the environment, which has led to a global economic and ecological emergency for insect pest control. Crude extracts of phytocompounds from Melia dubia Cav. were tested for their pesticidal effects on a certain enzyme cell line. An in silico molecular docking analysis of phytocompounds showed that the enzymes Glutathione S-Transferase (7RKA), Mytocontrial (5H3F), Acetylcholinesterase (7QAK), GABA receptor (7WGT), and DNA nucleotidylexotransferase (6GO4) interacted strongly with the phytocompounds. Compared to Dichlorvos and Malathion, the substances Guanosine (1) and Medroxyprogesterone (2) showed higher in-silico biopesticidal efficacy against Callosobruchus maculatus (Fab.). A silica gel column chromatographic technique was used to isolate Compounds 1 and 2. In vitro studies revealed that, after 96 hours, Guanosine (90.4% and LC50 value 5.63 mg/ml) caused the maximum toxicity of C. maculatus compared to the reference pesticides Dichlorvos (84.6% and LC50 value 5.94 mg/ml) and Malathion (92% and LC50 value 5.62 mg/ml). Comparing the results to the reference drugs, guanosine (1) showed potential as a pesticidal agent. Therefore, these particular compounds may provide alternative treatments that enhance the plants under investigation's historical use.

Brain acetylcholinesterase activity and the protective effect of Gac fruit on scopolamine-induced memory impairment in adult zebrafish

Gac fruit (Momordica cochinchinensis) belongs to the Cucurbitaceae family. This study aimed to investigate the anti-memory impairment effect of Gac fruit aril extract and brain acetylcholinesterase activity in adult zebrafish (Danio rerio). The behavioral test was performed using a color-biased appetite conditioning T-maze test and an inhibitory avoidance test to evaluate memory performance. The time spent in the green arm in the T-maze test was recorded, and latency time was recorded in the inhibitory avoidance test. Brain acetylcholinesterase (AChE) enzyme activity was measured using a 96-well microplate reader based on Ellman's method. Zebrafish that received rivastigmine and Gac extract had significantly increased time spent in the green arm and latency time when compared to the SCO group. Zebrafish that received rivastigmine and Gac fruit extract at 200 mg/kg had lower AChE activity than the SCO groups; however, there were no statistically significant differences between the groups. These findings suggest that Gac fruit extract has anti-memory impairment activity and may be beneficial for the development of health products to prevent Alzheimer’s disease.

Pnictogen bond-driven control of the molecular interaction between organophosphorus and acetylcholinesterase enzyme.

This study addresses a comprehensive assessment of the interaction between chemical warfare agents (CWA) and acetylcholinesterase (AChE) systems, focus on the intriguing pnictogen-bond interaction (PnB). Utilizing the crystallographic data from the Protein Data Bank pertaining to the AChE-CWA complex involving Sarin (GB), Cyclosarin (GF), 2-[fluoro(methyl)phosphoryl]oxy-1,1-dimethylcyclopentane (GP) and venomous agent X (VX) agents, the CWA is systematically displaced by increments of 0.1 Å along the PO bond axis, extending its distance by 4 Å from the original position. The AIM analysis was carried out and consistently revealed the presence of a significant interaction along the PO bond. Investigating the intrinsic nature of the PnB, the NBO and the EDA analysis unearthed the contribution of orbital factors to the overall energy of the system. Strikingly, this observation challenges the conventional σ-hole explanation commonly associated with such interactions. This finding adds a layer of complexity to understanding of PnB, encouraging further exploration into the underlying mechanisms governing these intriguing chemical phenomena.

Protective Effect of Ferulic Acid on Acetylcholinesterase and Amyloid Beta Peptide Plaque Formation in Alzheimer's Disease: An In Vitro Study.

Aim This study aims to comprehensively evaluate the effects of ferulic acid (FA) on acetylcholinesterase (AChE) enzyme activity and amyloid beta (Aβ) peptide plaque formation in an in vitro model of Alzheimer's disease (AD). Background ADis a progressive neurological condition marked by disrupted cholinergic signaling, accumulation of Aβ peptide, and tau protein hyperphosphorylation. Currently, no direct anti-Alzheimer drug that effectively prevents the cognitive decline from AD has been reported. To combat this, a multi-target drug addressing several molecular aspects would be ideal for AD. Natural compounds are preferred over synthetic drugs due to their accessibility, cost-efficiency, and lower toxicity The proven association between polyphenolconsumption and the prevention of AD has led to the investigation of the effect of FA, a polyphenolic compound, on acetylcholinesterase enzyme activity and Aβ peptide formation, the key targets of AD. Materials and method The free radical scavenging ability of FA was assessed by xanthine oxidase inhibitory activity. Furthermore, FA was also evaluated for its inhibitory activity against AChE enzyme and amyloid beta peptide formation to evaluate the neuroprotective potential of FA. Results The results showed that FA has the potential to be an AChE inhibitor, thus helping in blocking the activity of AChE and also reducing the incidence of amyloid beta plaque formation. Furthermore, the compound also exhibited a significant antioxidant property which was demonstrated by the xanthine oxidase enzyme inhibitory effect. Conclusion From the observed results, FA has significant antioxidant and neuroprotective effects which are compared with those of their respective standards. More research is required to determine the efficacy and safety of this compound as a treatment for neurodegenerative diseases like AD because the precise mechanism and degree of its AChE inhibitory effects in the brain are still elusive. A potent, selective, and effective drug is desperately needed to treat patients with AD and those at risk of developing the disease.

Biocontrol effects of chemical molecules derived from Beauveria bassiana against larvae of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae).

In this study, we conducted tests on the isolation, identification, characterization, and extraction of chemical molecules from Beauveria bassiana against Tuta absoluta larvae. The enzyme responses of T. absoluta to the crude extract were examined 24 h after treatment, and the number of dead larvae was calculated 24 and 48 h after treatment. Molecular docking studies were conducted to assess the interaction of important molecules with the acetylcholinesterase enzyme. The larvicidal activity of crude chemicals from fungi was high 24 h after treatment, with LC50 and LC90 values of 25.937 and 33.559 μg/mL, respectively. For a period of 48 h, the LC50 and LC90 values were 52.254 and 60.450 μg/mL, respectively. The levels of acetylcholinesterase, α-carboxylesterase, and β-carboxylesterase enzymes were lower in the treatment group after 24 h compared to the control group. The GC-MS test revealed that the crude extract consisted mainly of 9,10-octadecadienoic acid, which was the primary compound. Docking results indicated that 9,10-octadecadienoic acid showed a strong interaction with acetylcholinesterase (AChE). Our findings suggest that the chemical molecule 9,10-octadecadienoic acid derived from the entomopathogenic fungus B. bassiana is more toxic to T. absoluta larvae. We plan to conduct studies to test its effectiveness in semi-field conditions and to evaluate its stability in field conditions. We believe that this 9,10-octadecadienoic acid molecule could be used to control T. absoluta larvae in the near future without causing environmental pollution.

CG-MS, Radical Scavenging, Acetylcholinesterase Inhibition, Antifungal and Molecular Docking Studies of Essential Oil from the Leaves of Tapirira guianensis Aubl

The species Tapirira guianensis Aubl is used in folk medicine to treat leprosy, diarrhea, and syphilis. The present study aims to evaluate the chemical composition and the antioxidant, anticholinesterase, and antifungal potential of the essential oil from T. guianensis leaves. The plant material was collected at Arco Estadual do Cocó, with prior authorization from the Municipal Environment Department. The essential oil was extracted through the hydrodistillation process with a Clevenger-type apparatus, and the constituents were evaluated through Gas Chromatography coupled to Mass Spectrometry (GC-MS). The antioxidant potential was assessed through free radicals: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS+ (2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)) in a 96-well plate. Antifungal activity was evaluated using the Clinical Laboratory Standards Institute - M38-A protocol (CLSI, 2018). Gas chromatography coupled with mass spectrometry revealed the presence of constituents such as eugenol (59.00%), α-copaene (0.40%), β-caryophyllene (29.91%), α-humulene in T. guianensis. The essential oil demonstrated very promising antioxidant and anticholinesterase potential in In vitro studies. Molecular docking regarding acetylcholinesterase enzyme inhibition revealed that α-copaene has superior action compared to the drug physostigmine. The results of molecular docking for Candida albicans showed that α-copaene and α-humulene interacted in the same binding region as the PepA inhibitor against SAP5. This indicates their action is similar to the aspartic protease inhibitor, in addition to the possibility of a synergistic effect with the drug fluconazole. This is the first study of the biological potential of the essential oil from T. guianensis leaves, thus revealing its high potential for future studies in the scientific community. Therefore, we can infer that the essential oil of T. guianensis is a source of antioxidant, anticholinesterase, and antifungal constituents, with promising therapeutic potential in the management of Alzheimer's disease and Candida infections.

Assessment of Acetylcholinesterase Enzyme (AChE) Activity in the Developing Brain of TSD Lizard, Calotes Versicolor (Daud.)

Acetylcholinesterase (AChE) is a critical enzyme in the neuronal cholinergic system of vertebrates. It is one of the efficient cholinesterases that is involved in the termination of acetylcholine-mediated neurotransmission, rapidly hydrolyzing acetylcholine into acetate and choline. Barring a few reports on the distribution/presence of AChE enzyme activity in the adult reptilian species there are nil reports on the presence of this enzyme activity in the developing brain. Hence, the present investigation aims to evaluate AChE enzyme activity in the developing brain of an oviparous lizard, Calotes versicolor which exhibits a novel Female-Male-Female-Male (FMFM) pattern of temperature-dependent sex determination (TSD). The eggs were collected during breeding season, padded with moist cotton, and incubated in an incubator at 30o C. The whole brain from the embryos was collected during different developmental stages from oviposition (Stage 27) to hatching (stage 42). The AChE enzyme activity was quantified in the brain, according to Ellman’s protocol using a spectrophotometer. The findings reveal that the onset of AChE enzyme activity is observed as early as at oviposition, which reflects the early action of AChE activity in the developing brain. The observed results albeit indirectly suggest the involvement of AChE enzyme activity in the morphogenetic process. Further, an exponential increase in AChE activity during the post-gonadal differentiation phase indicates age-related elevation in AChE enzyme activity which in turn unveils its involvement in neuronal transmission of the embryonic brain. Besides, this specific AChE enzyme activity in the developing brain of Calotes versicolor represents a conserved pattern for the cholinergic system in vertebrates.

In Silico Investigation of Novel Compounds as Inhibitors of Acetylcholinesterase Enzyme for the Treatment of Alzheimer's Diseases.

Alzheimer's disease (AD) is a "progressive, neurodegenerative disease that occurs when nerve cells in the brain die." There are only 4 drugs approved by the United States Food and Drug Administration (FDA). Three (donepezil, rivastigmine, and galantamine) out of these four drugs are anticholinesterase inhibitors, while the fourth one memantine is an N-methyl-D-aspartate (NMDA) receptor inhibitor. Currently, two immunotherapy drugs that target amyloid protein (donanemab and lecanemab) are being considered for the treatment of Alzheimer's disease at an early stage. All these drug molecules are still not the complete answer to the treatment of Alzheimer's disease. A recent report from the Office of National Statistics showed that AD is the leading cause of death in 2022. Therefore, there is an urgency to develop more drugs that can treat AD. Based on this urgency, we aim to investigate how bioactive and already approved drugs could be repurposed for inhibiting the anticholinesterase enzyme using computational studies. To achieve this, the data science tool-Python coding was compiled on Jupyter Notebook to mine bioactive compounds from the ChEMBL database. The most bioactive compounds obtained were further investigated using Molecular Operating Environment (MOE) software to carry out molecular docking and ligand analysis, and this was followed by molecular dynamics simulation production at 35 ns using GROMACS 2022.4 on Archer 2 machine. The molecular dynamic analysis was carried out using HeroMDanalysis software. Data mining of the ChEMBL database was carried out for lipase inhibitors, and this gave CHEMBL-ID 1240685, a peptide molecule, the most active compound at the time of data mining. Further literature studies gave Zoladex an FDA-approved drug for the treatment of breast cancer as another compound of interest. The in silico studies were carried out against the anticholinesterase enzyme using two FDA-approved drugs donepezil and galantamine as a template for comparing the in silico activities of the repurposed drugs. A very useful receptor for this study was PDB-1DX6, a cocrystallized galantamine inhibitor of acetylcholinesterase enzyme. The molecular docking analysis (using ligand interactions) and molecular dynamic analysis (root mean square deviation (RMSD) and root mean square fluctuation (RMSF)) showed that the two peptide molecules CHEMBL-1240685 and Zoladex gave the best binding energy and stability when compared to the FDA-approved drugs (donepezil and galantamine). Finally, further literature studies revealed that Zoladex affects memory reduction; therefore, it was dropped as a possible repurposed drug. Our research showed that CHEMBL-1240685 is a potential compound that could be investigated for the inhibition of anticholinesterase enzyme and might be another drug molecule that could be used to treat Alzheimer's disease.

Content analysis, nanoparticle forming potential and acaricidal effects on Tick (Hyalomma marginatum) of essential oils from two common Thymbra species

In this study, the fatty acid, essential oil and aroma composition of Thymbra sintenisii Bornm. & Aznav. subsp. sintenisii Bornm. & Aznav (TSS) and Thymbra sintenisii Bornm. & Azn. subsp. isaurica P.H.Davis (TSI) were determined by GC-MS. The cytotoxic activity was determined with MTT assay and antioxidant activities were determined with DPPH, ABTS, CUPRAC methods. Urease, acetyl, butyryl, angiotensin, α-amylase, tyrosinase, elastase, and collagenase enzyme inhibition activities of these species were also determined. The acaricidal effects of essential oils from aerial parts of TSS and TSI on ticks and the nanoparticle formation potential of their essential oils with AgNO3 were determined and compared. The main components of TSS essential oil and aroma were determined as carvacrol and o-cemen (66.78 and 35.44%, respectively), the major components of TSI essential oil and aroma were carvacrol and γ-terpinene (63.78 and 31.44%, respectively). The species exhibited remarkably high antioxidant activity, particularly in the ABTS and CUPRAC methods. It was also determined that the butyrylcholinesterase and acetylcholinesterase enzyme inhibition activities (Inhibition%: 76.12±0.83 and 74.13±0.33, respectively) of the species were quite high. Moderate antimicrobial activity against the bacteria was observed for both essential oils, with MIC values ranging from 312 to 1250 μg/mL. Moreover, essential oils of these species showed good acaricidal activity on Hyalomma marginatum (LC50: 11.82 μg/mL for TSS; LC50: 57.64 μg/mL for TSI). The high antioxidant, anticholinesterase, and acaracidal activities observed in both species are attributed to the presence of carvacrol in their essential oils. The species have potential to be used in food supplements-preservatives, pharmaceutical industry.

African Under-Utilized Medicinal Leafy Vegetables Studied by Microtiter Plate Assays and High-Performance Thin-Layer Chromatography-Planar Assays.

Biological activities of six under-utilized medicinal leafy vegetable plants indigenous to Africa, i.e., Basella alba, Crassocephalum rubens, Gnetum africanum, Launaea taraxacifolia, Solanecio biafrae, and Solanum macrocarpon, were investigated via two independent techniques. The total phenolic content (TPC) was determined, and six microtiter plate assays were applied after extraction and fractionation. Three were antioxidant in vitro assays, i.e., ferric reducing antioxidant power (FRAP), cupric reduction antioxidant capacity (CUPRAC), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, and the others were enzyme (acetylcholinesterase, butyrylcholinesterase, and tyrosinase) inhibition assays. The highest TPC and antioxidant activity from all the methods were obtained from polar and medium polar fractions of C. rubens, S. biafrae, and S. macrocarpon. The highest acetyl- and butyrylcholinesterase inhibition was exhibited by polar fractions of S. biafrae, C. rubens, and L. taraxacifolia, the latter comparable to galantamine. The highest tyrosinase inhibition was observed in the n-butanol fraction of C. rubens and ethyl acetate fraction of S. biafrae. In vitro assay results of the different extracts and fractions were mostly in agreement with the bioactivity profiling via high-performance thin-layer chromatography-multi-imaging-effect-directed analysis, exploiting nine different planar assays. Several separated compounds of the plant extracts showed antioxidant, α-glucosidase, α-amylase, acetyl- and butyrylcholinesterase-inhibiting, Gram-positive/-negative antimicrobial, cytotoxic, and genotoxic activities. A prominent apolar bioactive compound zone was tentatively assigned to fatty acids, in particular linolenic acid, via electrospray ionization high-resolution mass spectrometry. The detected antioxidant, antimicrobial, antidiabetic, anticholinesterase, cytotoxic, and genotoxic potentials of these vegetable plants, in particular C. rubens, S. biafrae, and S. macrocarpon, may validate some of their ethnomedicinal uses.

Neuroprotective mechanism of trans,trans-Farnesol in an ICV-STZ-induced rat model of Alzheimer's pathology.

Alzheimer's disease (AD) is a prominent cause of dementia, resulting in neurodegeneration and memory impairment. This condition imposes a considerable public health burden on both patients and their families due to the patients' functional impairments as well as the psychological and financial constraints. It has been well demonstrated that its aetiology involves proteinopathy, mitochondriopathies, and enhanced reactive oxygen species (ROS) generation, which are some of the key features of AD brains that further result in oxidative stress, excitotoxicity, autophagy, and mitochondrial dysfunction. The current investigation was created with the aim of elucidating the neurological defence mechanism of trans,trans-Farnesol (TF) against intracerebroventricular-streptozotocin (ICV-STZ)-induced Alzheimer-like symptoms and related pathologies in rodents. The current investigation involved male SD rats receiving TF (25-100mg/kg, per oral) consecutively for 21days in ICV-STZ-treated animals. An in silico study was carried out to explore the possible interaction between TF and NADH dehydrogenase and succinate dehydrogenase. Further, various behavioural (Morris water maze and novel object recognition test), biochemical (oxidants and anti-oxidant markers), activities of mitochondrial enzyme complexes and acetylcholinesterase (AChE), pro-inflammatory (tumor necrosis factor-alpha; TNF-α) levels, and histopathological studies were evaluated in specific brain regions. Rats administered ICV-STZ followed by treatment with TF (25, 50, and 100mg/kg) for 21days had significantly better mental performance (reduced escape latency to access platform, extended time spent in target quadrant, and improved differential index) in the Morris water maze test and new object recognition test models when compared to control (ICV-STZ)-treated groups. Further, TF treatment significantly restored redox proportion, anti-oxidant levels, regained mitochondrial capacities, attenuated altered AChE action, levels of TNF-α, and histopathological alterations in certain brain regions in comparison with control. In in silico analysis, TF caused greater interaction with NADH dehydrogenase and succinate dehydrogenase. The current work demonstrates the neuroprotective ability of TF in an experimental model with AD-like pathologies. The study further suggests that the neuroprotective impacts of TF may be related to its effects on TNF-α levels, oxidative stress pathways, and mitochondrial complex capabilities.

Design, synthesis, and evaluation of novel bistrifluoromethyl-based hydrazones as dual inhibitors of acetylcholinesterase and carbonic anhydrase enzymes for Alzheimer's disease.

In this project, non-sulfonamide bistrifluoromethyl-derived hydrazide-hydrazones were synthesized as multi-target-directed ligands to treat Alzheimer's disease and then, the novel derivatives were characterized by diverse spectral methods. Acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) inhibitory qualifications of these compounds were determined. The reported compounds (2a-y) were determined to be effective inhibitors of the hCA I, hCA II and AChE enzymes with Ki values in the range of 1.130 ± 0.15-5.440 ± 0.93 μM for hCA I, 0.894 ± 0.05-6.647 ± 1.35 μM for hCA II, and 0.196 ± 0.03-4.222 ± 1.04 μM for AChE. In silico studies were also performed to illuminate the binding interactions.