Displaying publications 1 - 20 of 96 in total

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  1. Salleh WMNHW, Salihu AS, Ab Ghani N
    Nat Prod Res, 2024;38(4):629-633.
    PMID: 36794425 DOI: 10.1080/14786419.2023.2180507
    This study was designed to examine the essential oils compositions of Litsea glauca Siebold and Litsea fulva Fern.-Vill. growing in Malaysia. The essential oils were achieved by hydrodistillation and fully characterized by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The study identified 17 and 19 components from the leaf oils from L. glauca (80.7%) and L. fulva (81.5%), respectively. The major components of L. glauca oil were β-selinene (30.8%), β-calacorene (11.3%), tridecanal (7.6%), isophytol (4.8%) and β-eudesmol (4.5%); whereas in L. fulva oil gave β-caryophyllene (27.8%), caryophyllene oxide (12.8%), α-cadinol (6.3%), (E)-nerolidol (5.7%), β-selinene (5.5%) and tridecanal (5.0%). Anticholinesterase activity was evaluated using Ellman method. The essential oils showed moderate inhibitory activity on acetylcholinesterase and butyrylcholinesterase assays. Our findings demonstrate that the essential oil could be very useful for the characterization, pharmaceutical, and therapeutic applications of the essential oil from the genus Litsea.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology
  2. Ado MA, Maulidiani M, Ismail IS, Ghazali HM, Shaari K, Abas F
    Nat Prod Res, 2021 Sep;35(17):2992-2996.
    PMID: 31631709 DOI: 10.1080/14786419.2019.1679138
    Phytochemical investigation on the soluble fractions of n-hexane and dichloromethane of methanolic leaves extract of the Callicarpa maingayi K. & G. led to the isolation of three triterpenoids [euscaphic acid (1), arjunic acid (2), and ursolic acid (3)] together with two flavones [apigenin (4) and acacetin (5)], two phytosterols [stigmasterol 3-O-β-glycopyranoside (6) and sitosterol 3-O-β-glycopyranoside (7)], and a fatty acid [n-hexacosanoic acid (8)]. Six (6) compounds (1, 2, 3, 4, 5, and 8) are reported for the first time from this species. Their structures were elucidated and identified by extensive NMR techniques, GC-MS and comparison with the previously reported literature. Compound 3 was found to displayed good inhibition against acetylcholinesterase with an IC50 value of 21.5 ± 0.022 μM, while 1 and 2 exhibited pronounced α-glucosidase inhibitory activity with IC50 values of 22.4 ± 0.016 μM and 24.9 ± 0.012 μM, respectively.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  3. Abbasi MA, Rehman A, Siddiqui SZ, Hadi N, Mumtaz A, Shah SAA, et al.
    Pak J Pharm Sci, 2019 Jan;32(1):61-68.
    PMID: 30772791
    In the current research work, a series of new N-(alkyl/aralkyl)-N-(2,3-dihydro-1,4-benzodioxan-6-yl)-4-chlorobenzenesulfonamides has been synthesized by reacting 1,4-benzozzdioxan-6-amine (1) with 4-chlorobenzenesulfonyl chloride (2) to yield N-(2,3-dihydro-1,4-benzodioxan-6-yl)-4-chlorobenzenesulfonamide (3) which was further reacted with different alkyl/aralkyl halides (4a-n) to afford the target compounds (5a-n). Structures of the synthesized compounds were confirmed by IR, 1H-NMR, EI-MS spectral techniques and CHN analysis data. The results of enzyme inhibition showed that the molecules, N-2-phenethyl-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5j) and N-(1-butyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5d), exhibited moderate inhibitory potential against acetylcholinesterase with IC50 values 26.25±0.11 μM and 58.13±0.15 μM respectively, whereas, compounds N-benzyl-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5i) and N-(pentane-2-yl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-chlorobenzenesulfonamide (5f) showed moderate inhibition against α-glucosidase enzyme as evident from IC50 values 74.52±0.07 and 83.52±0.08 μM respectively, relative to standards Eserine having IC50 value of 0.04±0.0001 μM for cholinesterases and Acarbose having IC50 value 38.25±0.12 μM for α-glucosidase, respectively.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  4. Mani V, Parle M, Ramasamy K, Abdul Majeed AB
    J Sci Food Agric, 2011 Jan 15;91(1):186-92.
    PMID: 20848667 DOI: 10.1002/jsfa.4171
    Coriandrum sativum L., commonly known as coriander and belonging to the family Apiaceae (Umbelliferae), is cultivated throughout the world for its nutritional value. The present study was undertaken to investigate the effects of fresh Coriandrum sativum leaves (CSL) on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. In this study, CSL (5, 10 and 15% w/w of diet) was fed orally with a specially prepared diet for 45 days consecutively to experimental animals. Elevated plus-maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam, scopolamine and ageing-induced amnesia served as the interoceptive behavioral models.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology
  5. Salleh WMNHW, Khamis S, Nafiah MA, Abed SA
    Nat Prod Res, 2021 Jun;35(11):1887-1892.
    PMID: 31293176 DOI: 10.1080/14786419.2019.1639183
    This study was designed to examine the chemical composition and anticholinesterase inhibitory activity of the essential oil of Pseuduvaria macrophylla (Oliv.) Merr. (Annonaceae) from Malaysia. The essential oil was obtained by hydrodistillation and fully analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The analysis led to the identification of thirty-four chemical components that represented 87.7 ± 0.5% of the total oil. The essential oil was found to be rich in germacrene D (21.1 ± 0.4%), bicyclogermacrene (10.5 ± 0.5%), δ-cadinene (5.6 ± 0.2%), α-copaene (5.1 ± 0.3%), and α-cadinol (5.0 ± 0.3%). Anticholinesterase activity was evaluated using Ellman method. The essential oil showed weak inhibitory activity against acetylcholinesterase (I%: 32.5%) and butyrylcholinesterase (I%: 35.4%) assays. Our findings demonstrate that the essential oil could be very useful for the characterization, pharmaceutical and therapeutic applications of the essential oil from Pseuduvaria macrophylla.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  6. Ali Hassan SH, Fry JR, Abu Bakar MF
    Biomed Res Int, 2013;2013:138950.
    PMID: 24288662 DOI: 10.1155/2013/138950
    Garcinia parvifolia belongs to the same family as mangosteen (Garcinia mangostana), which is known locally in Sabah as "asam kandis" or cherry mangosteen. The present study was conducted to determine the phytochemicals content (total phenolic, flavonoid, anthocyanin, and carotenoid content) and antioxidant and acetylcholinesterase inhibition activity of the flesh and peel of G. parvifolia. All samples were freeze-dried and extracted using 80% methanol and distilled water. For the 80% methanol extract, the flesh of G. parvifolia displayed higher phenolic and flavonoid contents than the peel, with values of 7.2 ± 0.3 mg gallic acid equivalent (GAE)/g and 5.9 ± 0.1 mg rutin equivalent (RU)/g, respectively. Anthocyanins were detected in the peel part of G. parvifolia but absent in the flesh. The peel of G. parvifolia displayed higher total carotenoid content as compared to the flesh part with the values of 17.0 ± 0.3 and 3.0 ± 0.0 mg β-carotene equivalents (BC)/100 g, respectively. The free-radical scavenging, ferric reducing, and acetylcholinesterase inhibition effect of the flesh were higher as compared to the peel in both extracts. These findings suggested that the edible part of G. parvifolia fruit has a potential as a natural source of antioxidant and anti-Alzheimer's agents.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  7. 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/pharmacology*
  8. 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/pharmacology
  9. Saleem H, Htar TT, Naidu R, Ahmad I, Zengin G, Ahmad M, et al.
    J Pharm Biomed Anal, 2019 Mar 20;166:128-138.
    PMID: 30640043 DOI: 10.1016/j.jpba.2019.01.007
    In this study, different solvent extracts (methanol, dichloromethane and n-hexane) from aerial and stem parts of Buxus papillosa C.K. Schneid (Buxaceae) were investigated for a panoply of bioassays. Biological profiles were established by determining antioxidant and enzyme inhibition profiles. Toxicity was tested using MTT cell viability assay on five different human cancer cell lines i.e, MCF-7, MDA-MB-231, CaSki, DU-145 and SW-480. For chemical fingerprinting, total bioactive contents and UHPLC-MS secondary metabolites profile were determined. Generally, both aerial and stem methanol extracts had highest total bioactive contents, radical scavenging and reducing power potential. DCM and n-hexane extracts were found to be most active for total antioxidant and metal chelating activity. The UHPLC-MS analysis of methanol extracts revealed the presence of several phenolic, flavonoid, alkaloid, saponin and depsipeptide derivatives. All the extracts were significantly active against butyrylcholinesterase, whereas moderate inhibition was observed for acetylcholinesterase, α-glucosidase and urease. Similarly, a considerable level of cytotoxicity was observed against all the tested cell lines with IC50 values ranging from 26 to 225.9 μg/mL. Aerial methanol and stem n-hexane extracts were found to be most cytotoxic. Principal component analysis was also performed to find any possible correlation between biological activities and total bioactive contents. On the basis of our findings, B. papillosa may be considered as promising source of bioactive molecules.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology
  10. Saleem H, Zengin G, Khan KU, Ahmad I, Waqas M, Mahomoodally FM, et al.
    Nat Prod Res, 2021 Feb;35(4):664-668.
    PMID: 30919661 DOI: 10.1080/14786419.2019.1587427
    This study sets out to probe into total bioactive contents, UHPLC-MS secondary metabolites profiling, antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum and metal chelating) and enzyme inhibitory (acetylcholinesterase- AChE, butyrylcholinesterase- BChE, α-amylase, α glucosidase, and tyrosinase) activities of methanol extract of Aerva javanica, also known as desert cotton or Kapok bush. Aerva javanica contains considerable phenolic (44.79 ± 3.12 mg GAE/g) and flavonoid (28.86 ± 0.12 mg QE/g) contents which tends to correlate with its significant antioxidant potential for ABTS, FRAP and CUPRAC assays with values of 101.41 ± 1.18, 124.10 ± 1.71 and 190.22 ± 5.70 mg TE/g, respectively. The UHPLC-MS analysis identified the presence of 45 phytochemicals belonging to six major groups: phenolic, flavonoids, lignin, terpenes, glycoside and alkaloid. Moreover, the plant extract also showed potent inhibitory action against AChE (3.73 ± 0.22 mg GALAE/g), BChE (3.31 ± 0.19 mg GALAE/g) and tyrosinase (126.05 ± 1.77 mg KAE/g). The observed results suggest A. javanica could be further explored as a natural source of bioactive compounds.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology
  11. Ahmad H, Ahmad S, Shah SAA, Khan HU, Khan FA, Ali M, et al.
    J Asian Nat Prod Res, 2018 Feb;20(2):172-181.
    PMID: 28463565 DOI: 10.1080/10286020.2017.1319820
    New lycoctonine-type dual cholinesterase inhibitor, swatinine-C (1), along with three known norditerpenoid alkaloids, hohenackerine (2), aconorine (5) and lappaconitine (6) and two synthetically known but phytochemically new benzene derivatives, methyl 2-acetamidobenzoate (3) and methyl 4-[2-(methoxycarbonyl)anilino]-4-oxobutanoate (4), was isolated from the roots of A. laeve. Structures of new and known compounds (1-6) were established on the basis of latest spectroscopic techniques and by close comparison with the data available in literature. In vitro, compounds (1-6) were tested against AChE and BChE inhibitory activities. Compounds 1 and 2 showed competitive inhibition against AChE (IC50 = 3.7 μM, 4.53 μM) and BChE (IC50 = 12.23 μM, 9.94 μM), respectively. Compounds 5 and 6 showed promising noncompetitive type of inhibitory profile against AChE (IC50 = 2.51 and 6.13 μM) only. Compounds 3 and 4 showed weak inhibitory profile against both AChE and BChE.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  12. Ahmad H, Ahmad S, Shah SAA, Latif A, Ali M, Khan FA, et al.
    Bioorg Med Chem, 2017 07 01;25(13):3368-3376.
    PMID: 28457693 DOI: 10.1016/j.bmc.2017.04.022
    Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6β-Methoxy, 9β-dihydroxylheteratisine (1), 1α,11,13β-trihydroxylhetisine (2), 6,15β-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  13. Ahmad H, Ahmad S, Ali M, Latif A, Shah SAA, Naz H, et al.
    Bioorg Chem, 2018 08;78:427-435.
    PMID: 29698893 DOI: 10.1016/j.bioorg.2018.04.008
    Three new norditerpenoids alkaloids, 1β-hydroxy,14β-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1-5 were established on the basis of HR-EIMS, 1H and 13C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1-5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed non-competitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  14. Anwar F, Saleem U, Ahmad B, Ashraf M, Rehman AU, Froeyen M, et al.
    Comput Biol Chem, 2020 Dec;89:107378.
    PMID: 33002716 DOI: 10.1016/j.compbiolchem.2020.107378
    Neurodegenerative diseases have complex etiology and pose a challenge to scientists to develop simple and cost-effective synthetic compounds as potential drug candidates for such diseases. Here, we report an extension of our previously published in silico screening, where we selected four new compounds as AChE inhibitors. Further, based on favorable binding possess, MD simulation and MMGBSA, two most promising compounds (3a and 3b) were selected, keeping in view the ease of synthesis and cost-effectiveness. Due to the critical role of BChE, LOX and α-glucosidase in neurodegeneration, the selected compounds were also screened against these enzymes. The IC50 values of 3a against AChE and BChE found to be 12.53 and 352.42 μM, respectively. Moderate to slight inhibitions of 45.26 % and 28.68 % were presented by 3a against LOX and α-glucosidase, respectively, at 0.5 mM. Insignificant inhibitions were observed with 3b against the four selected enzymes. Further, in vivo trial demonstrated that 3a could significantly diminish AChE levels in the mice brain as compared to the control. These findings were in agreement with the histopathological analysis of the brain tissues. The results corroborate that selected compounds could serve as a potential lead for further development and optimization as AChE inhibitors to achieve cost-effective anti-Alzheimer's drugs.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  15. 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/pharmacology*
  16. Abbasi MA, Anwar A, Rehman A, Siddiqui SZ, Rubab K, Shah SAA, et al.
    Pak J Pharm Sci, 2017 Sep;30(5):1715-1724.
    PMID: 29084694
    Heterocyclic molecules have been frequently investigated to possess various biological activities during the last few decades. The present work elaborates the synthesis and enzymatic inhibition potentials of a series of sulfonamides. A series of 1-arylsulfonyl-4-Phenylpiperazine (3a-n) geared up by the reaction of 1-phenylpiperazine (1) and different (un)substituted alkyl/arylsulfonyl chlorides (2a-n), under defined pH control using water as a reaction medium. The synthesized molecules were characterized by 1H-NMR, 13C-NMR, IR and EI-MS spectral data. The enzyme inhibition study was carried on α-glucosidase, lipoxygenase (LOX), acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE) enzymes supported by docking simulation studies and the IC50 values rendered a few of the synthesized molecules as moderate inhibitors of these enzymes where, the compound 3e exhibited comparatively better potency against α-glucosidase enzyme. The synthesized compounds showed weak or no inhibition against LOX, AChE and BChE enzymes.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology
  17. Basiri A, Murugaiyah V, Osman H, Kumar RS, Kia Y, Awang KB, et al.
    Eur J Med Chem, 2013 Sep;67:221-9.
    PMID: 23871902 DOI: 10.1016/j.ejmech.2013.06.054
    Series of hitherto unreported piperidone grafted pyridopyrimidines synthesized through ionic liquid mediated multi-component reaction. These compounds were evaluated for their inhibitory activities against AChE and BChE enzymes. All the compounds displayed considerable potency against AChE with IC50 values ranging from 0.92 to 9.11 μM, therein compounds 6a, 6h and 6i displayed superior enzyme inhibitory activities compared to standard drug with IC50 values of 0.92, 1.29 and 2.07 μM. Remarkably, all the compounds displayed higher BChE inhibitory activity compared to galantamine with IC50 values of 1.89-8.13 μM. Molecular modeling, performed for the most active compounds using three dimensional crystal structures of TcAChE and hBChE, disclosed binding template of these inhibitors into the active site of their respective enzymes.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  18. Bukhari SN, Jantan I, Masand VH, Mahajan DT, Sher M, Naeem-ul-Hassan M, et al.
    Eur J Med Chem, 2014 Aug 18;83:355-65.
    PMID: 24980117 DOI: 10.1016/j.ejmech.2014.06.034
    A series of novel carbonyl compounds was synthesized by a simple, eco-friendly and efficient method. These compounds were screened for anti-oxidant activity, in vitro cytotoxicity and for inhibitory activity for acetylcholinesterase and butyrylcholinesterase. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. Among them, compound 14 exhibited strong free radical scavenging activity (18.39 μM) while six compounds (1, 3, 4, 13, 14, and 19) were found to be the most protective against Aβ-induced neuronal cell death in PC12 cells. Compounds 4 and 14, containing N-methyl-4-piperidone linker, showed high acetylcholinesterase inhibitory activity as compared to reference drug donepezil. Molecular docking and QSAR (Quantitative Structure-Activity Relationship) studies were also carried out to determine the structural features that are responsible for the acetylcholinesterase and butyrylcholinesterase inhibitory activity.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology
  19. Liew SY, Khaw KY, Murugaiyah V, Looi CY, Wong YL, Mustafa MR, et al.
    Phytomedicine, 2015 Jan 15;22(1):45-8.
    PMID: 25636869 DOI: 10.1016/j.phymed.2014.11.003
    Nine monoterpenoid indole alkaloids; naucletine (1), angustidine (2), nauclefine (3), angustine (4), naucline (5), angustoline (6), harmane (7), 3,14-dihydroangustoline (8), strictosamide (9) and one quinoline alkaloid glycoside; pumiloside (10) from Nauclea officinalis were tested for cholinesterase inhibitory activity. All the alkaloids except for pumiloside (10) showed strong to weak BChE inhibitory effect with IC50 values ranging between 1.02-168.55 μM. Angustidine (2), nauclefine (3), angustine (4), angustoline (6) and harmane (7) showed higher BChE inhibiting potency compared to galanthamine. Angustidine (2) was the most potent inhibitor towards both AChE and BChE. Molecular docking (MD) studies showed that angustidine (2) docked deep into the bottom gorge of hBChE and formed hydrogen bonding with Ser 198 and His 438. Kinetic study of angustidine (2) on BChE suggested a mixed inhibition mode with an inhibition constant (Ki) of 6.12 μM.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  20. Abdul Wahab SM, Sivasothy Y, Liew SY, Litaudon M, Mohamad J, Awang K
    Bioorg Med Chem Lett, 2016 08 01;26(15):3785-92.
    PMID: 27236720 DOI: 10.1016/j.bmcl.2016.05.046
    A new acylphenol, malabaricone E (1) together with the known malabaricones A-C (2-4), maingayones A and B (5 and 6) and maingayic acid B (7) were isolated from the ethyl acetate extract of the fruits of Myristica cinnamomea King. Their structures were determined by 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Compounds 3 (1.84±0.19 and 1.76±0.21μM, respectively) and 4 (1.94±0.27 and 2.80±0.49μM, respectively) were identified as dual inhibitors, with almost equal acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibiting potentials. The Lineweaver-Burk plots of compounds 3 and 4 indicated that they were mixed-mode inhibitors. Based on the molecular docking studies, compounds 3 and 4 interacted with the peripheral anionic site (PAS), the catalytic triad and the oxyanion hole of the AChE. As for the BChE, while compound 3 interacted with the PAS, the catalytic triad and the oxyanion hole, compound 4 only interacted with the catalytic triad and the oxyanion hole.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
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