Displaying publications 1 - 20 of 85 in total

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  1. Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation
    Zha GF, Zhang CP, Qin HL, Jantan I, Sher M, Amjad MW, et al.
    Bioorg Med Chem, 2016 05 15;24(10):2352-9.
    PMID: 27083471 DOI: 10.1016/j.bmc.2016.04.015
    A series of new α,β-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aβ1-42 aggregation. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aβ1-42 aggregation. The compound 3o exhibited best AChE (IC50=0.037μM) inhibitory potential. Furthermore, compound 3o disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aβ aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aβ-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  2. Medroxyprogesterone derivatives from microbial transformation as anti-proliferative agents and acetylcholineterase inhibitors (combined in vitro and in silico approaches)
    Yusop SNW, Imran S, Adenan MI, Sultan S
    Steroids, 2020 12;164:108735.
    PMID: 32976918 DOI: 10.1016/j.steroids.2020.108735
    The fungal transformations of medroxyrogesterone (1) were investigated for the first time using Cunninghamella elegans, Trichothecium roseum, and Mucor plumbeus. The metabolites obtained are as following: 6β, 20-dihydroxymedroxyprogesterone (2), 12β-hydroxymedroxyprogesterone (3), 6β, 11β-dihydroxymedroxyprogesterone (4), 16β-hydroxymedroxyprogesterone (5), 11α, 17-dihydroxy-6α-methylpregn-4-ene-3, 20-dione (6), 11-oxo-medroxyprogesterone (7), 6α-methyl-17α-hydroxypregn-1,4-diene-3,20-dione (8), and 6β-hydroxymedroxyprogesterone (9), 15β-hydroxymedroxyprogesterone (10), 6α-methyl-17α, 11β-dihydroxy-5α-pregnan-3, 20-dione (11), 11β-hydroxymedroxyprogesterone (12), and 11α, 20-dihydroxymedroxyprogesterone (13). Among all the microbial transformed products, the newly isolated biotransformed product 13 showed the most potent activity against proliferation of SH-SY5Y cells. Compounds 12, 5, 6, 9, 11, and 3 (in descending order of activity) also showed some extent of activity against SH-SY5Y tumour cell line. The never been reported biotransformed product, 2, showed the most potent inhibitory activity against acetylcholinesterase. Molecular modelling studies were carried out to understand the observed experimental activities, and also to obtain more information on the binding mode and the interactions between the biotransformed products, and enzyme.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  3. Fulltext Anticholinesterase inhibitory activity of quaternary alkaloids from Tinospora crispa
    Yusoff M, Hamid H, Houghton P
    Molecules, 2014 Jan 20;19(1):1201-11.
    PMID: 24448061 DOI: 10.3390/molecules19011201
    Quaternary alkaloids are the major alkaloids isolated from Tinospora species. A previous study pointed to the necessary presence of quaternary nitrogens for strong acetylcholinesterase (AChE) inhibitory activity in such alkaloids. Repeated column chromatography of the vine of Tinospora crispa extract led to the isolation of one new protoberberine alkaloid, 4,13-dihydroxy-2,8,9-trimethoxydibenzo[a,g]quinolizinium (1), along with six known alkaloids-dihydrodiscretamine (2), columbamine (3), magnoflorine (4), N-formylannonaine (5), N-formylnornuciferine (6), and N-trans-feruloyltyramine (7). The seven compounds were isolated and structurally elucidated by spectroscopic analysis. Two known alkaloids, namely, dihydrodiscretamine and columbamine are reported for the first time for this plant. The compounds were tested for AChE inhibitory activity using Ellman's method. In the AChE inhibition assay, only columbamine (3) showed strong activity with IC50 48.1 µM. The structure-activity relationships derived from these results suggest that the quaternary nitrogen in the skeleton has some effect, but that a high degree of methoxylation is more important for acetylcholinesterase inhibition.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  4. Synthesis, characterization, and molecular docking analysis of novel benzimidazole derivatives as cholinesterase inhibitors
    Yoon YK, Ali MA, Wei AC, Choon TS, Khaw KY, Murugaiyah V, et al.
    Bioorg Chem, 2013 Aug;49:33-9.
    PMID: 23886696 DOI: 10.1016/j.bioorg.2013.06.008
    Two series of novel acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors containing benzimidazole core structure were synthesized by a four-step reaction pathway starting from 4-fluoro-3-nitrobenzoic acid as the basic compound. The structure of the novel benzimidazoles was characterized and confirmed by the elemental and mass spectral analyses as well as (1)H NMR spectroscopic data. Of the 34 novel synthesized compounds, three benzimidazoles revealed AChE inhibition with IC50<10 μM. The highest inhibitory activity (IC50=5.12 μM for AChE and IC50=8.63 μM for BChE) corresponds to the compound 5IIc (ethyl 1-(3-(1H-imidazol-1-yl)propyl)-2-(4-nitrophenyl)-1H-benzo[d]imidazole-5-carboxylate). The relationship between lipophilicity and the chemical structures as well as their limited structure-activity relationship was discussed.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  5. 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*
  6. 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
  7. 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
  8. Xanthone: Potential Acetylcholinesterase Inhibitor for Alzheimer's Disease Treatment
    Vanessa VV, Mah SH
    Mini Rev Med Chem, 2021;21(17):2507-2529.
    PMID: 33583373 DOI: 10.2174/1389557521666210212152514
    Alzheimer's disease is a neurodegenerative disorder that results in progressive and irreversible central nervous system impairment, which has become one of the severe issues recently. The most successful approach of Alzheimer's treatment is the administration of cholinesterase inhibitors to prevent the hydrolysis of acetylcholine and subsequently improve cholinergic postsynaptic transmission. This review highlights a class of heterocycles, namely xanthone, and its remarkable acetylcholinesterase inhibitory activities. Naturally occurring xanthones, including oxygenated, prenylated, pyrano, and glycosylated xanthones, exhibited promising inhibition effects towards acetylcholinesterase. Interestingly, synthetic xanthone derivatives with complex substituents such as alkyl, pyrrolidine, piperidine, and morpholine have shown greater acetylcholinesterase inhibition activities. The structure-activity relationship of xanthones revealed that the type and position of the substituent(s) attached to the xanthone moiety influenced acetylcholinesterase inhibition activities where hydrophobic moiety will lead to an improved activity by contributing to the π-π interactions, as well as the hydroxy substituent(s) by forming hydrogen-bond interactions. Thus, further studies, including quantitative structure-activity relationship, in vivo and clinical validation studies are crucial for the development of xanthones into novel anti-Alzheimer's disease drugs.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  9. Assessment of Clarias batrachus as a source of acetylcholinesterase (AchE) for the detection of insecticides
    Tham LG, Perumal N, Syed MA, Shamaan NA, Shukor MY
    J Environ Biol, 2009 Jan;30(1):135-8.
    PMID: 20112875
    An inhibitive assay of insecticides using Acetylcholinesterase (AChE) from the local fish Clarias batrachus is reported. AChE was assayed according to the modified method of Ellman. Screening of insecticide and heavy metals showed that carbofuran and carbaryl strongly inhibited C. batrachus AChE. The inhibition concentration (IC) IC50 values (and the 95% confidence interval) for both carbofuran and carbaryl inhibition on C. batrachus AChE at 6.66 (5.97-7.52) and 130.00 (119.3-142.5) microg l(-1), respectively was within the IC50 range of Electrophorus electricus at 6.20 (6.03-6.39) and 133.01 (122.40-145.50) microg l(-1), respectively and were much lower than bovine AChE at 20.94 (19.53-22.58) and 418.80 (390.60-451.60) microg l(-1), respectively. The results showed that C. batrachus have the potential to be used as a cheaper and more readily available source of AChE than other more commercially available sources.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  10. New cholinesterase inhibitors from Garcinia atroviridis
    Tan WN, Khairuddean M, Wong KC, Khaw KY, Vikneswaran M
    Fitoterapia, 2014 Sep;97:261-7.
    PMID: 24924287 DOI: 10.1016/j.fitote.2014.06.003
    A triflavanone, Garcineflavanone A (1) and a biflavonol, Garcineflavonol A (2) have been isolated from the stem bark of Garcinia atroviridis (Clusiaceae), collected in Peninsular Malaysia. Their structures were established using one and two-dimensional NMR, UV, IR and mass spectrometry and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activity. Molecular docking studies of the isolated compounds were performed using docking procedure of AutoDock to disclose the binding interaction and orientation of these molecules into the active site gorge.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  11. Synthesis, in vitro biological screening and docking study of benzo[d]oxazole bis Schiff base derivatives as a potent anti-Alzheimer agent
    Taha M, Rahim F, Zaman K, Anouar EH, Uddin N, Nawaz F, et al.
    J Biomol Struct Dyn, 2023 Mar;41(5):1649-1664.
    PMID: 34989316 DOI: 10.1080/07391102.2021.2023640
    We have synthesized benzo[d]oxazole derivatives (1-21) through a multistep reaction. Alteration in the structure of derivatives was brought in the last step via using various substituted aromatic aldehydes. In search of an anti-Alzheimer agent, all derivatives were evaluated against acetylcholinesterase and butyrylcholinesterase enzyme under positive control of standard drug donepezil (IC50 = 0.016 ± 0.12 and 4.5 ± 0.11 µM) respectively. In case of acetylcholinesterase enzyme inhibition, derivatives 8, 9 and 18 (IC50 = 0.50 ± 0.01, 0.90 ± 0.05 and 0.3 ± 0.05 µM) showed very promising inhibitory potentials. While in case of butyrylcholinesterase enzyme inhibition, most of the derivatives like 6, 8, 9, 13, 15, 18 and 19 (IC50 = 2.70 ± 0.10, 2.60 ± 0.10, 2.20 ± 0.10, 4.25 ± 0.10, 3.30 ± 0.10, 0.96 ± 0.05 and 3.20 ± 0.10 µM) displayed better inhibitory potential than donepezil. Moreover, derivative 18 is the most potent one among the series in both inhibitions. The binding interaction of derivatives with the active gorge of the enzyme was confirmed via a docking study. Furthermore, the binding interaction between derivatives and the active site of enzymes was correlated through the SAR study. Structures of all derivatives were confirmed through spectroscopic techniques such as 1H-NMR, 13C-NMR and HREI-MS, respectively.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  12. Synthesis and discovery of novel hexacyclic cage compounds as inhibitors of acetylcholinesterase
    Suresh Kumar R, Ashraf Ali M, Osman H, Ismail R, Choon TS, Yoon YK, et al.
    Bioorg Med Chem Lett, 2011 Jul 1;21(13):3997-4000.
    PMID: 21621414 DOI: 10.1016/j.bmcl.2011.05.003
    Hexacyclic derivatives share vital pharmacological properties, considered useful in Alzheimer's disease. The aim of this study was synthesis and its evaluation for acetyl cholinesterase inhibitory activity of novel hexacyclic analogues. Compound 4f, showed potent inhibitory activity against acetyl cholinesterase enzyme with IC(50) 0.72 μmol/L.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  13. Fulltext Analogues of 2'-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase
    Sukumaran SD, Nasir SB, Tee JT, Buckle MJC, Othman R, Rahman NA, et al.
    J Enzyme Inhib Med Chem, 2021 Dec;36(1):130-137.
    PMID: 33243025 DOI: 10.1080/14756366.2020.1847100
    A series of C4-substituted tertiary nitrogen-bearing 2'-hydroxychalcones were designed and synthesised based on a previous mixed type acetylcholinesterase inhibitor. Majority of the 2'-hydroxychalcone analogues displayed a better inhibition against acetylcholinesterase (AChE) than butyrylcholinesterase (BuChE). Among them, compound 4c was identified as the most potent AChE inhibitor (IC50: 3.3 µM) and showed the highest selectivity for AChE over BuChE (ratio >30:1). Molecular docking studies suggested that compound 4c interacts with both the peripheral anionic site (PAS) and catalytic anionic site (CAS) regions of AChE. ADMET analysis confirmed the therapeutic potential of compound 4c based on its blood-brain barrier penetrating. Overall, the results suggest that this 2'-hydroxychalcone deserves further investigation into the therapeutic lead for Alzheimer's disease (AD).
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  14. Fulltext Synthesis, Biological Evaluation and Molecular Modelling of 2'-Hydroxychalcones as Acetylcholinesterase Inhibitors
    Sukumaran SD, Chee CF, Viswanathan G, Buckle MJ, Othman R, Abd Rahman N, et al.
    Molecules, 2016 Jul 22;21(7).
    PMID: 27455222 DOI: 10.3390/molecules21070955
    A series of 2'-hydroxy- and 2'-hydroxy-4',6'-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE). The majority of the compounds were found to show some activity, with the most active compounds having IC50 values of 40-85 µM. Higher activities were generally observed for compounds with methoxy substituents in the A ring and halogen substituents in the B ring. Kinetic studies on the most active compounds showed that they act as mixed-type inhibitors, in agreement with the results of molecular modelling studies, which suggested that they interact with residues in the peripheral anionic site and the gorge region of AChE.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  15. Multitarget drug design strategy in Alzheimer's disease: focus on cholinergic transmission and amyloid-β aggregation
    Simoni E, Bartolini M, Abu IF, Blockley A, Gotti C, Bottegoni G, et al.
    Future Med Chem, 2017 06;9(10):953-963.
    PMID: 28632446 DOI: 10.4155/fmc-2017-0039
    AIM: Alzheimer pathogenesis has been associated with a network of processes working simultaneously and synergistically. Over time, much interest has been focused on cholinergic transmission and its mutual interconnections with other active players of the disease. Besides the cholinesterase mainstay, the multifaceted interplay between nicotinic receptors and amyloid is actually considered to have a central role in neuroprotection. Thus, the multitarget drug-design strategy has emerged as a chance to face the disease network.

    METHODS: By exploiting the multitarget approach, hybrid compounds have been synthesized and studied in vitro and in silico toward selected targets of the cholinergic and amyloidogenic pathways.

    RESULTS: The new molecules were able to target the cholinergic system, by joining direct nicotinic receptor stimulation to acetylcholinesterase inhibition, and to inhibit amyloid-β aggregation.

    CONCLUSION: The compounds emerged as a suitable starting point for a further optimization process.

    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  16. Chemical composition and anticholinesterase inhibitory activity of Pavetta graciliflora Wall. ex Ridl. essential oil
    Salleh WMNHW, Khamis S
    Z Naturforsch C J Biosci, 2020 Nov 26;75(11-12):467-471.
    PMID: 32469335 DOI: 10.1515/znc-2020-0075
    Chemical composition and anticholinesterase activity of the essential oil of Pavetta graciliflora Wall. ex Ridl. (Rubiaceae) was examined for the first time. The essential oil was obtained by hydrodistillation and was fully characterized by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). A total of 20 components were identified in the essential oil, which made up 92.85% of the total oil. The essential oil is composed mainly of β-caryophyllene (42.52%), caryophyllene oxide (25.33%), β-pinene (8.67%), and α-pinene (6.52%). The essential oil showed weak inhibitory activity against acetylcholinesterase (AChE) (I%: 62.5%) and butyrylcholinesterase (BChE) (I%: 65.4%) assays. Our findings were shown to be very useful for the characterization, pharmaceutical, and therapeutic applications of the essential oil from P. graciliflora.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  17. 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
  18. 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
  19. Anti-Cholinesterase Activity of Chalcone Derivatives: Synthesis, In Vitro Assay and Molecular Docking Study
    Riswanto FDO, Rawa MSA, Murugaiyah V, Salin NH, Istyastono EP, Hariono M, et al.
    Med Chem, 2021;17(5):442-452.
    PMID: 31808389 DOI: 10.2174/1573406415666191206095032
    BACKGROUND: Chalcones, originated from natural product, have been broadly studied their biological activity against various proteins which at the molecular level, are responsible for the progress of the diseases in cancer (e.g. kinases), inflammation (oxidoreductases), atherosclerosis (cathepsins receptor), and diabetes (e.g. α-glucosidase).

    OBJECTIVE: Here we synthesize 10 chalcone derivatives to be evaluated their in vitro enzymatic inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).

    METHODS: The synthesis was carried out using Claissen-Schimdt condensation and the in vitro assay was conducted using Ellman Method.

    RESULTS: Compounds 2b and 4b demonstrated as the best IC50 of 9.3 μM and 68.7 μM respectively, towards AChE and BChE inhibition. Molecular docking studies predicted that this activity might be due to the interaction of the chalcones with important amino acid residues in the binding site of AChE such as SER200 and in that of BChE, such as TRP82, SER198, TRP430, TYR440, LEU286 and VAL288.

    CONCLUSION: Chalcone can be used as the scaffold for cholinesterase inhibitor, in particularly either fluorine or nitro group to be augmented at the para-position of Ring B, whereas the hydrophobic chain is necessary at the meta-position of Ring B.

    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  20. 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*
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