Displaying publications 41 - 60 of 85 in total

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  1. Fulltext Insecticidal activity and the mechanism of action of three phenylpropanoids isolated from the roots of Piper sarmentosum Roxb
    Hematpoor A, Liew SY, Azirun MS, Awang K
    Sci Rep, 2017 10 03;7(1):12576.
    PMID: 28974710 DOI: 10.1038/s41598-017-12898-z
    Hexane, dichloromethane and methanol extracts of the roots of Piper sarmentosum Roxb. were screened for toxicity towards Sitophilus oryzae (L.), Rhyzopertha dominica (F.), and Plodia interpunctella (Hübner) and the hexane extract exhibited the highest mortality percentage. Bioassay-guided fractionation of the hexane extract resulted in the isolation of asaricin 1, isoasarone 2, and trans-asarone 3. Asaricin 1 and isoasarone 2 were the most toxic compounds to Sitophilus oryzae, Rhyzopertha dominica, and Plodia interpunctella. Sitophilus oryzae and Rhyzopertha dominica exposed to asaricin 1 and isoasarone 2 required the lowest median lethal time. Insecticidal activity of trans-asarone 3 showed consistent toxicity throughout the 60 days towards all three insects as compared to asaricin 1 and isoasarone 2. Asaricin 1 and isoasarone 2 at different doses significantly reduced oviposition and adult emergence of the three insects in treated rice. Trans-asarone 3 had lowest toxicity with highest LC and LT values in all tested insects relative to its mild oviposition inhibition and progeny activity. Moreover, asaricin 1 and isoasarone 2 significantly inhibited acetylcholinesterase in comparison with trans-asarone 3 and the control. Acetylcholinesterase inhibition of Rhyzopertha dominica and Plodia interpunctella by asaricin 1 and isoasarone 2 were lower than that of Sitophilus oryzae, which correlated with their higher resistance.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  2. Inhibitory effect of asiatic acid on acetylcholinesterase, excitatory post synaptic potential and locomotor activity
    Nasir MN, Abdullah J, Habsah M, Ghani RI, Rammes G
    Phytomedicine, 2012 Feb 15;19(3-4):311-6.
    PMID: 22112723 DOI: 10.1016/j.phymed.2011.10.004
    The asiatic acid, a triterpenoids isolated from Centella asiatica was used to delineate its inhibitory effect on acetylcholinesterase (AChE) properties, excitatory post synaptic potential (EPSP) and locomotor activity. This study is consistent with asiatic acid having an effect on AChE, a selective GABA(B) receptor agonist and no sedative effect on locomotor.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  3. In vitro evaluation and in silico screening of synthetic acetylcholinesterase inhibitors bearing functionalized piperidine pharmacophores
    Brahmachari G, Choo C, Ambure P, Roy K
    Bioorg Med Chem, 2015 Aug 01;23(15):4567-4575.
    PMID: 26105711 DOI: 10.1016/j.bmc.2015.06.005
    A series of densely functionalized piperidine (FP) scaffolds was synthesized following a diastereoselective one-pot multicomponent protocol under eco-friendly conditions. The FPs were evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activity, and in silico studies for all the target compounds were carried out using pharmacophore mapping, molecular docking and quantitative structure-activity relationship (QSAR) analysis in order to understand the structural features required for interaction with the AChE enzyme and the key active site residues involved in the intermolecular interactions. Halogenation, nitration or 3,4-methylenedixoxy-substitution at the phenyl ring attached to the 2- and 6-positions of 1,2,5,6-tetrahydropyridine nucleus in compounds 14-17, 19, 20, 24 and 26 greatly enhanced the AChE inhibitory activity. The docking analysis demonstrated that the inhibitors are well-fitted in the active sites. The in silico studies enlighten the future course of studies in modifying the scaffolds for better therapeutic efficacy against the deadly Alzheimer's disease.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  4. In silico studies, synthesis and pharmacological evaluation to explore multi-targeted approach for imidazole analogues as potential cholinesterase inhibitors with neuroprotective role for Alzheimer's disease
    Gurjar AS, Darekar MN, Yeong KY, Ooi L
    Bioorg Med Chem, 2018 05 01;26(8):1511-1522.
    PMID: 29429576 DOI: 10.1016/j.bmc.2018.01.029
    Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple factors associated with its pathogenesis. Our strategy against AD involves design of multi-targeted 2-substituted-4,5-diphenyl-1H-imidazole analogues which can interact and inhibit AChE, thereby, increasing the synaptic availability of ACh, inhibit BuChE, relieve induced oxidative stress and confer a neuroprotective role. Molecular docking was employed to study interactions within the AChE active site. In silico ADME study was performed to estimate pharmacokinetic parameters. Based on computational studies, some analogues were synthesized and subjected to pharmacological evaluation involving antioxidant activity, toxicity and memory model studies in animals followed by detailed mechanistic in vitro cholinesterase inhibition study. Amongst the series, analogue 13 and 20 are the most promising multi-targeted candidates which can potentially increase memory, decrease free radical levels and protect neurons against cognitive deficit.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  5. In silico studies, nitric oxide, and cholinesterases inhibition activities of pyrazole and pyrazoline analogs of diarylpentanoids
    Mohd Faudzi SM, Leong SW, Auwal FA, Abas F, Wai LK, Ahmad S, et al.
    Arch Pharm (Weinheim), 2021 Jan;354(1):e2000161.
    PMID: 32886410 DOI: 10.1002/ardp.202000161
    A new series of pyrazole, phenylpyrazole, and pyrazoline analogs of diarylpentanoids (excluding compounds 3a, 4a, 5a, and 5b) was pan-assay interference compounds-filtered and synthesized via the reaction of diarylpentanoids with hydrazine monohydrate and phenylhydrazine. Each analog was evaluated for its anti-inflammatory ability via the suppression of nitric oxide (NO) on IFN-γ/LPS-activated RAW264.7 macrophage cells. The compounds were also investigated for their inhibitory capability toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), using a modification of Ellman's spectrophotometric method. The most potent NO inhibitor was found to be phenylpyrazole analog 4c, followed by 4e, when compared with curcumin. In contrast, pyrazole 3a and pyrazoline 5a were found to be the most selective and effective BChE inhibitors over AChE. The data collected from the single-crystal X-ray diffraction analysis of compound 5a were then applied in a docking simulation to determine the potential binding interactions that were responsible for the anti-BChE activity. The results obtained signify the potential of these pyrazole and pyrazoline scaffolds to be developed as therapeutic agents against inflammatory conditions and Alzheimer's disease.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  6. Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies
    Chigurupati S, Selvaraj M, Mani V, Selvarajan KK, Mohammad JI, Kaveti B, et al.
    Bioorg Chem, 2016 08;67:9-17.
    PMID: 27231830 DOI: 10.1016/j.bioorg.2016.05.002
    The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68±0.13μM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77±0.25μM and IC50: 12.59±0.21μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74±0.09μM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52±0.62μM and IC50: 13.13±0.85μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  7. HPTLC based approach for bioassay-guided evaluation of antidiabetic and neuroprotective effects of eight essential oils of the Lamiaceae family plants
    Romero Rocamora C, Ramasamy K, Meng Lim S, Majeed ABA, Agatonovic-Kustrin S
    J Pharm Biomed Anal, 2020 Jan 30;178:112909.
    PMID: 31618702 DOI: 10.1016/j.jpba.2019.112909
    A high-performance thin-layer chromatography (HPTLC) method combined with effect-directed-analysis (EDA) was developed to screen the antioxidant, neuroprotective and antidiabetic effects in essential oils derived from lavender flower, lemon myrtle, oregano, peppermint, sage, and rosemary leaves (Lamiaceae family). HPTLC hyphenated with microchemical (DPPH•, p-anisaldehyde, and ferric chloride) derivatizations, was used to evaluate antioxidant activity, presence of phytosterols and terpenoids, and polyphenolic content, while the combination with biochemical (α-amylase and acetylcholine esterase (AChE) enzymatic) derivatizations was used to asses α-amylase and AChE inhibitory activities. The superior antioxidant activity of oregano leaf extract is attributed to the presence of high levels of aromatic compounds, like polyphenolic acids. The strongest α-amylase inhibition was observed in lemon myrtle and rosemary plus extracts due to the presence of monoterpenes. Rosemary and sage extracts exhibit the highest AChE inhibition activity, with 1 μL essential oils being more potent than the recommended daily dose of donepezil. This superior neuroprotection was attributed to the presences of di- and triterpenes that displayed strong AChE inhibition and antioxidant potential in DPPH• free radical assay. Antioxidant activity was related to phenolic content (R = 0.49), while α-amylase inhibitory activity was positively related to antioxidant activity (R = 0.20) and terpenoid/sterol content (R = 0.31). AChE inhibitory activity was correlated (R = 0.80) to the combined effect of phenolics and terpenoids. Thus, the superior AChE inhibitory and neuroprotection potential of rosemary and sage essential oils could be attributed to joint effects of main phenolic and terpene constituents. The hyphenated HPTLC method provided rapid bioanalytical profiling of highly complex essential oil samples.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  8. Exploration of synthetic multifunctional amides as new therapeutic agents for Alzheimer's disease through enzyme inhibition, chemoinformatic properties, molecular docking and dynamic simulation insights
    Hassan M, Abbasi MA, Aziz-Ur-Rehman, Siddiqui SZ, Hussain G, Shah SAA, et al.
    J Theor Biol, 2018 12 07;458:169-183.
    PMID: 30243565 DOI: 10.1016/j.jtbi.2018.09.018
    A new series of multifunctional amides has been synthesized having moderate enzyme inhibitory potentials and mild cytotoxicity. 2-Furyl(1-piperazinyl)methanone (1) was coupled with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (2) to form {4-[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]-1-piperazinyl}(2-furyl)methanone (3). Different elecrophiles were synthesized by the reaction of various un/substituted anilines (4a-o) with 2-bromoacetylbromide (5), 2‑bromo‑N-(un/substituted-phenyl)acetamides (6a-o). Further, equimolar ratios of 3 and 6a-o were allowed to react in the presence of K2CO3 in acetonitrile to form desired multifunctional amides (7a-o). The structural confirmation of all the synthesized compounds was carried out by their EI-MS, IR, 1H NMR and 13C NMR spectral data. Enzyme inhibition activity was performed against acetyl and butyrylcholinestrase enzymes, whereby 7e showed very good activity having IC50 value of 5.54 ± 0.03 and 9.15 ± 0.01 μM, respectively, relative to eserine, a reference standard. Hemolytic activity of the molecules was checked to asertain their cytotoxicity towards red blood cell membrance and it was observed that most of the compounds were not toxic up to certain range. Moreover, chemoinformatic protepties and docking simulation results also showed the significance of 7e as compared to other compounds. Based on in vitro and in silico analysis 7e could be used as a template for the development of new drugs against Alzheimer's disease.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  9. Ethyl nitrobenzoate: A novel scaffold for cholinesterase inhibition
    Yeong KY, Liew WL, Murugaiyah V, Ang CW, Osman H, Tan SC
    Bioorg Chem, 2017 02;70:27-33.
    PMID: 27863748 DOI: 10.1016/j.bioorg.2016.11.005
    A series of novel cholinesterase inhibitors containing nitrobenzoate core structure were synthesized by a facile and efficient method. The structure of the novel compounds were fully characterized and confirmed by analytical as well as spectroscopic methods. Compound indicated as 2f was found to possess the best cholinesterase inhibitory activities of all the evaluated compounds. Results suggest that 2f is a selective acetylcholinesterase inhibitor, although it also inhibits butyrylcholinesterase at higher concentration. Kinetics inhibition result suggest that 2f is a mixed-mode inhibitor of acetylcholinesterase. In addition, it was found to have low cytotoxicity. Molecular docking on compound 2f was carried out to rationalize the observed in vitro enzymatic assay results. Most importantly, the potential of nitrobenzoate derivatives as cholinesterase inhibitor was shown through this study. In summary, we discovered nitrobenzoates as a new scaffold that may eventually yield useful compounds in treatment of Alzheimer's disease.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  10. Efficient Synthesis and Discovery of Schiff Bases as Potent Cholinesterase Inhibitors
    Razik BM, Osman H, Ezzat MO, Basiri A, Salhin A, Kia Y, et al.
    Med Chem, 2016;12(6):527-36.
    PMID: 26833077
    BACKGROUND: The search for new cholinesterase inhibitors is still a promising approach for management of Alzheimer`s disease. Schiff bases are considered as important class of organic compounds, which have wide range of applications including as enzyme inhibitors. In the present study, a new green ionic liquid mediated strategy was developed for convenient synthesis of two series of Schiff bases 3(a-j) and 5(a-j) as potential cholinesterase inhibitors using aromatic aldehydes and primary amines in [bmim]Br.

    METHODS: The synthesized compounds were evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential by modified Ellman's method. The molecular interactions between the most active compound and the enzyme were analyzed by molecular docking.

    RESULTS: Among them, 3j displayed higher inhibitory activities than reference drug, galanthamine, with IC50 values of 2.05 and 5.77 µM, for AChE and BChE, respectively. Interestingly, all the compounds except 3b displayed higher BChE inhibitions than galanthamine with IC50 values ranging from 5.77 to 18.52 µM. Molecular docking of compound 3j inside the TcAChE and hBChE completely coincided with the inhibitory activities observed. The compound forms strong hydrogen bonding at the peripheral anionic site of AChE whereas on BChE, it had hydrophobic and mild polar interactions.

    CONCLUSION: An efficient and eco-friendly synthetic methodology has been developed to synthesize Schiff bases in a very short reaction time and excellent yields in ionic solvent, whereby the compounds from series 3 showed promising cholinesterase inhibitory activity.

    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  11. Effect of polymer, plasticizer and filler on orally disintegrating film
    Liew KB, Tan YT, Peh KK
    Drug Dev Ind Pharm, 2014 Jan;40(1):110-9.
    PMID: 23311593 DOI: 10.3109/03639045.2012.749889
    Difficulty in swallowing tablets or capsules has been identified as one of the contributing factors to non-compliance of geriatric patients. Although orally disintegrating tablet was designed for fast disintegration in mouth, the fear of taking solid tablets and the risk of choking for certain patient populations still exist.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  12. Designing of promising medicinal scaffolds for Alzheimer's disease through enzyme inhibition, lead optimization, molecular docking and dynamic simulation approaches
    Hassan M, Abbasi MA, Aziz-Ur-Rehman, Siddiqui SZ, Shahzadi S, Raza H, et al.
    Bioorg Chem, 2019 10;91:103138.
    PMID: 31446329 DOI: 10.1016/j.bioorg.2019.103138
    In the designed research work, a series of 2-furoyl piperazine based sulfonamide derivatives were synthesized as therapeutic agents to target the Alzheimer's disease. The structures of the newly synthesized compounds were characterized through spectral analysis and their inhibitory potential was evaluated against butyrylcholinesterase (BChE). The cytotoxicity of these sulfonamides was also ascertained through hemolysis of bovine red blood cells. Furthermore, compounds were inspected by Lipinki Rule and their binding profiles against BChE were discerned by molecular docking. The protein fluctuations in docking complexes were recognized by dynamic simulation. From our in vitro and in silico results 5c, 5j and 5k were identified as promising lead compounds for the treatment of targeted disease.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  13. Design, synthesis, anti-acetylcholinesterase evaluation and molecular modelling studies of novel coumarin-chalcone hybrids
    Hasan AH, Shakya S, Hussain FHS, Murugesan S, Chander S, Pratama MRF, et al.
    J Biomol Struct Dyn, 2023;41(21):11450-11462.
    PMID: 36591704 DOI: 10.1080/07391102.2022.2162583
    The major enzyme responsible for the hydrolytic breakdown of the neurotransmitter acetylcholine (ACh) is acetylcholinesterase (AChE). Acetylcholinesterase inhibitors (AChEIs) are the most prescribed class of medications for the treatment of Alzheimer's disease (AD) and dementia. The limitations of available therapy, like side effects, drug tolerance, and inefficacy in halting disease progression, drive the need for better, more efficacious, and safer drugs. In this study, a series of fourteen novel chalcone-coumarin derivatives (8a-n) were designed, synthesized and characterized by spectral techniques like FT-IR, NMR, and HR-MS. Subsequently, the synthesized compounds were tested for their ability to inhibit acetylcholinesterase (AChE) activity by Ellman's method. All tested compounds showed AChE inhibition with IC50 value ranging from 0.201 ± 0.008 to 1.047 ± 0.043 μM. Hybrid 8d having chloro substitution on ring-B of the chalcone scaffold showed relatively better potency, with IC50 value of 0.201 ± 0.008 μM compared to other members of the series. The reference drug, galantamine, exhibited an IC50 at 1.142 ± 0.027 μM. Computational studies revealed that designed compounds bind to the peripheral anionic site (PAS), the catalytic active site (CAS), and the mid-gorge site of AChE. Putative binding modes, ligand-enzyme interactions, and stability of the best active compound are studied using molecular docking, followed by molecular dynamics (MD) simulations. The cytotoxicity of the synthesised derivatives was determined using the MTT test at three concentrations (100 g/mL, 500 g/mL, and 1 mg/mL). None of the chemicals had a significant effect on the body at the highest dose of 1 mg/mL.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  14. Design, synthesis and biological evaluation of novel carbamates as potential inhibitors of acetylcholinesterase and butyrylcholinesterase
    Wu J, Pistolozzi M, Liu S, Tan W
    Bioorg Med Chem, 2020 03 01;28(5):115324.
    PMID: 32008882 DOI: 10.1016/j.bmc.2020.115324
    Rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), has been approved by U.S. Food and Drug Administration to treat Alzheimer's disease (AD) and Parkinson's disease (PD) dementia. In the current work, a bambuterol derivative lacking one of the carbamoyloxy groups on the benzene ring (BMC-1) and its analogues were synthesized using 1-(3-hydroxyphenyl) ethan-1-one and 1-(4-hydroxyphenyl) ethan-1-one as starting materials. In-vitro cholinesterase assay established that nine compounds were more potent to inhibit both electric eel AChE and equine serum BChE than rivastigmine under the same experimental conditions. Further study confirmed that among the nine carbamates, BMC-3 (IC50(AChE) = 792 nM, IC50(BChE) = 2.2 nM) and BMC-16 (IC50(AChE) = 266 nM, IC50(BChE) = 10.6 nM) were excellent cholinesterase inhibitors with potential of permeating through the blood-brain barrier. These carbamates could be used as potential dual inhibitors of AChE and BChE and to discover novel drugs for the treatment of AD and PD dementia.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  15. Deep eutectic solvent mediated synthesis of 3,4-dihydropyrimidin-2(1H)-ones and evaluation of biological activities targeting neurodegenerative disorders
    Saleem Khan M, Asif Nawaz M, Jalil S, Rashid F, Hameed A, Asari A, et al.
    Bioorg Chem, 2022 01;118:105457.
    PMID: 34798458 DOI: 10.1016/j.bioorg.2021.105457
    Substitution of hazardous and often harmful organic solvents with "green" and "sustainable" alternative reaction media is always desirous. Ionic liquids (IL) have emerged as valuable and versatile liquids that can replace most organic solvents in a variety of syntheses. However, recently new types of low melting mixtures termed as Deep Eutectic Solvents (DES) have been utilized in organic syntheses. DES are non-volatile in nature, have sufficient thermal stability, and also have the ability to be recycled and reused. Hence DES have been used as alternative reaction media to perform different organic reactions. The availability of green, inexpensive and easy to handle alternative solvents for organic synthesis is still scarce, hence our interest in DES mediated syntheses. Herein we have investigated Biginelli reaction in different DES for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Monoamine oxidases and cholinesterases are important drug targets for the treatment of various neurological disorders such as Alzheimer's disease, Parkinson's disease, depression and anxiety. The compounds synthesized herein were evaluated for their inhibitory potential against these enzymes. Some of the compounds were found to be highly potent and selective inhibitors. Compounds 1 h and 1c were the most active monoamine oxidase A (MAO A) (IC50 = 0.31 ± 0.11 µM) and monoamine oxidase B (MAO B) (IC50 = 0.34 ± 0.04 µM) inhibitors respectively. All compounds were selective AChE inhibitors and did not inhibit BChE (<29% inhibition). Compound 1 k (IC50 = 0.13 ± 0.09 µM) was the most active AChE inhibitor.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  16. Fulltext Combining In Silico and In Vitro Studies to Evaluate the Acetylcholinesterase Inhibitory Profile of Different Accessions and the Biomarker Triterpenes of Centella asiatica
    Jusril NA, Muhamad Juhari ANN, Abu Bakar SI, Md Saad WM, Adenan MI
    Molecules, 2020 Jul 24;25(15).
    PMID: 32721993 DOI: 10.3390/molecules25153353
    Alzheimer's disease (AD) is a neurodegenerative disease and the most cause of dementia in elderly adults. Acetylcholinesterase (AChE) is an important beneficial target for AD to control cholinergic signaling deficit. Centella asiatica (CA) has proven to be rich with active ingredients for memory enhancement. In the present study, the chemical profiling of three accession extracts of CA namely SECA-K017, SECA-K018, and, SECA-K019 were performed using high-performance liquid chromatography (HPLC). Four biomarker triterpene compounds were detected in all CA accessions. Quantitative analysis reveals that madecassoside was the highest triterpene in all the CA accessions. The biomarker compounds and the ethanolic extracts of three accessions were investigated for their acetylcholinesterase (AChE) inhibitory activity using Ellman's spectrophotometer method. The inhibitory activity of the triterpenes and accession extracts was compared with the standard AChE inhibitor eserine. The results from the in vitro study showed that the triterpene compounds exhibited an AChE inhibitory activity with the half-maximal inhibitory concentration (IC50) values between 15.05 ± 0.05 and 59.13 ± 0.18 µg/mL. Asiatic acid was found to possess strong AChE inhibitory activity followed by madecassic acid. Among the CA accession extracts, SECA-K017 and SECA-K018 demonstrated a moderate AChE inhibitory activity with an IC50 value of 481.5 ± 0.13 and 763.5 ± 0.16 µg/mL, respectively from the in silico docking studies, it is observed that asiatic acid and madecassic acid showed very good interactions with the active sites and fulfilled docking parameters against AChE. The present study suggested that asiatic acid and madecassic acid in the CA accessions could be responsible for the AChE inhibitory action and could be used as markers to guide further studies on CA as potential natural products for the treatment of AD.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  17. Cholinesterase inhibitory triterpenoids from the bark of Garcinia hombroniana
    Jamila N, Khairuddean M, Yeong KK, Osman H, Murugaiyah V
    J Enzyme Inhib Med Chem, 2015 Feb;30(1):133-9.
    PMID: 24666300 DOI: 10.3109/14756366.2014.895720
    Context: Garcinia hombroniana Pierre, known as manggis hutan in Malaysia is a rich source of xanthones and benzophenones.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  18. Cholinesterase inhibitory activity versus aromatic core multiplicity: a facile green synthesis and molecular docking study of novel piperidone embedded thiazolopyrimidines
    Basiri A, Murugaiyah V, Osman H, Kumar RS, Kia Y, Hooda A, et al.
    Bioorg Med Chem, 2014 Jan 15;22(2):906-16.
    PMID: 24369842 DOI: 10.1016/j.bmc.2013.11.020
    Novel thiazolopyrimidine derivatives have been synthesized via microwave assisted, domino cascade methodology in ionic liquid and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Among the newly synthesized compounds 6d, 6a, 6e and 6b displayed higher AChE inhibitory activity than standard drug, galanthamine, with IC50 values of 0.53, 1.47, 1.62 and 2.05μM, respectively. Interestingly, all the compounds except for 6m-r and 6x displayed higher BChE inhibitory potentials than galanthamine with IC50 values ranging from 1.09 to 18.56μM. Molecular docking simulations for 6d possessing the most potent AChE and BChE inhibitory activities, disclosed its binding interactions at the active site gorge of AChE and BChE enzymes.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  19. Cholinesterase inhibitory activity of isoquinoline alkaloids from three Cryptocarya species (Lauraceae)
    Wan Othman WNN, Liew SY, Khaw KY, Murugaiyah V, Litaudon M, Awang K
    Bioorg Med Chem, 2016 09 15;24(18):4464-4469.
    PMID: 27492195 DOI: 10.1016/j.bmc.2016.07.043
    Alzheimer's disease is the most common form of dementia among older adults. Acetylcholinesterase and butyrylcholinesterase are two enzymes involved in the breaking down of the neurotransmitter acetylcholine. Inhibitors for these enzymes have potential to prolong the availability of acetylcholine. Hence, the search for such inhibitors especially from natural products is needed in developing potential drugs for Alzheimer's disease. The present study investigates the cholinesterase inhibitory activity of compounds isolated from three Cryptocarya species towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Nine alkaloids were isolated; (+)-nornantenine 1, (-)-desmethylsecoantofine 2, (+)-oridine 3, (+)-laurotetanine 4 from the leaves of Cryptocarya densiflora BI., atherosperminine 5, (+)-N-methylisococlaurine 6, (+)-N-methyllaurotetanine 7 from the bark of Cryptocarya infectoria Miq., 2-methoxyatherosperminine 8 and (+)-reticuline 9 from the bark of Cryptocarya griffithiana Wight. In general, most of the alkaloids showed higher inhibition towards BChE as compared to AChE. The phenanthrene type alkaloid; 2-methoxyatherosperminine 8, exhibited the most potent inhibition against BChE with IC50 value of 3.95μM. Analysis of the Lineweaver-Burk (LB) plot of BChE activity over a range of substrate concentration suggested that 2-methoxyatherosperminine 8 exhibited mixed-mode inhibition with an inhibition constant (Ki) of 6.72μM. Molecular docking studies revealed that 2-methoxyatherosperminine 8 docked well at the choline binding site and catalytic triad of hBChE (butyrylcholinesterase from Homo sapiens); hydrogen bonding with Tyr 128 and His 438 residues respectively.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  20. Fulltext Cholinesterase enzymes inhibitors from the leaves of Rauvolfia reflexa and their molecular docking study
    Fadaeinasab M, Hadi AH, Kia Y, Basiri A, Murugaiyah V
    Molecules, 2013 Mar 25;18(4):3779-88.
    PMID: 23529036 DOI: 10.3390/molecules18043779
    Plants of the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders. Rauvolfia reflexa, a member of the family, has been used as an antidote for poisons and to treat malaria. The dichloromethane, ethanol and methanol extracts from the leaves of Rauvolfia reflexa showed potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, with IC50 values in the 8.49 to 52.23 g/mL range. Further cholinesterase inhibitory-guided isolation of these extracts afforded four bioactive compounds, namely: (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (1), (E)-methyl 3-(4-hydroxy-3,5-dimethoxyphenyl) acrylate (2), 17-methoxycarbonyl-14-heptadecaenyl-4-hydroxy-3-methoxycinnamate (3) and 1,2,3,4-tetrahydro-1-oxo-β-carboline (4). The isolated compounds showed moderate cholinesterase inhibitory activity compared to the reference standard, physostigmine. Compounds 1 and 2 showed the highest inhibitory activity against AChE (IC50 = 60.17 µM) and BChE (IC50 = 61.72 µM), respectively. Despite having similar molecular weight, compounds 1 and 2 were structurally different according to their chemical substitution patterns, leading to their different enzyme inhibition selectivity. Compound 2 was more selective against BChE, whereas compound 1 was a selective inhibitor of AChE. Molecular docking revealed that both compounds 1 and 2 were inserted, but not deeply into the active site of the cholinesterase enzymes.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
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