Displaying publications 1 - 20 of 165 in total

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  1. Fulltext Anti-snake venom and methanolic extract of Andrographis paniculata: a multipronged strategy to neutralize Naja naja venom acetylcholinesterase and hyaluronidase
    Nayak AG, Kumar N, Shenoy S, Roche M
    3 Biotech, 2020 Nov;10(11):476.
    PMID: 33083200 DOI: 10.1007/s13205-020-02462-4
    The study investigates the ability of methanolic extract of Andrographis paniculata (MAP) to supplement polyvalent anti-snake venom (ASV) in inhibiting neurotoxic enzyme acetylcholinesterase (AChE) and 'spreading factor' hyaluronidase from Naja naja (N.N) venom. AChE and hyaluronidase activity were measured in 100 or 200 µg of crude venom, respectively, and designated as 'control'. In Test Group I, enzyme assays were performed immediately after the addition of ASV/MAP/ASV + MAP to the venom. Inhibition of AChE by ASV (100-367 µg) was 12-17%, and of hyaluronidase (22-660 µg) was 33-41%. Under the same conditions, MAP (100-400 µg) inhibited AChE and hyaluronidase to the extent of 17-33% and 17-52%, respectively. When ASV (220 µg) and MAP (100-200 µg) were added together, AChE and hyaluronidase were inhibited to a greater extent from 39-63 to 36-44%, than when either of them was used alone. In Test Group 2, the venom was incubated with ASV/MAP/ASV + MAP for 10-30 min at 37 °C prior to the assay which enhanced AChE inhibition by 6%, 82% and 18% respectively, when compared to Test Group I. Though there was no change in inhibition of hyaluronidase in the presence of ASV, MAP could further increase the extent of inhibition by 27% and ASV + MAP upto 4%. In Test Group III, venom and substrate were incubated for 90 min and hyaluronidase activity was measured after the addition of inhibitors. Here, ASV + MAP caused increased inhibition by 69% compared to ASV alone. The study confirms the ability of phytochemicals in MAP to contribute to a multipronged strategy by supplementing, thereby augmenting the efficacy of ASV.
    Matched MeSH terms: Cholinesterase Inhibitors
  2. In vitro anticholinergic and antihistaminic activities of Acorus calamus Linn. leaves extracts
    Vijayapandi P, Annabathina V, SivaNagaSrikanth B, Manjunath V, Boggavarapu P, Mohammed P AK, et al.
    Afr J Tradit Complement Altern Med, 2012;10(1):95-101.
    PMID: 24082330
    The present investigation was aimed at determining the effects of hexane, acetone, methanol and aqueous extracts of Acorus calamus leaves (ACHE, ACAE, ACME and ACAQE) on cholinergic and histaminic system using isolated frog rectus abdominis muscle and guinea pig ileum. A dose dependent potentiation of Ach response (anticholinesterase like effect) was found with ACAE and ACME at 0.25, 0.5, 0.75 and 1 mg/ml, but at higher dose of ACAE, ACME, ACAQE and ACHE (5, 20 mg/ml) inhibit the Ach response (antinicotinic effect). These results revealed biphasic effect of Acorus calamus leaves extracts on acetylcholine induced contractile response in isolated frog rectus abdominis muscle preparation (i.e. potentiation effect at lower dose and inhibitory effect at higher dose). Studies on isolated guinea pig ileum demonstrated antihistaminic effect in a dose dependent manner (100-1000 µg/ml) with ACAE, ACME and ACAQE. In addition, the dose dependent inhibition of Ach response (antimuscarinic effect) was observed with ACAE and ACME. In conclusion, Acorus calamus leaves extracts exerts antinicotinic, anticholinesterase like activities in isolated frog rectus abdominis muscle and antihistaminic, antimuscarinic effect in guinea pig ileum. It has been suggested that these observed activities can be further studied for therapeutic potential of Acorus calamus leaves in the treatment of cognitive disorders and asthma.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  3. Fulltext Use of Potentially Inappropriate Medications in People With Dementia in Vietnam and Its Associated Factors
    Nguyen TA, Pham T, Vu HTT, Nguyen TX, Vu TT, Nguyen BTT, et al.
    Am J Alzheimers Dis Other Demen, 2018 Nov;33(7):423-432.
    PMID: 29642720 DOI: 10.1177/1533317518768999
    This study examined the use of potentially inappropriate medicines that may affect cognition (PIMcog) in people with dementia and its associated factors. Medical records of all outpatients with dementia attending a tertiary hospital in Vietnam between January 1, 2015, and December 31, 2016, were examined. Medicine use was assessed against a list of PIMcog. Variables associated with having a PIMcog were assessed using a multiple logistic regression. Of the 128 patients, 41% used a PIMcog, 39.1% used cholinesterase inhibitors (CEIs) concomitantly with anticholinergics, and 18% used antipsychotics. The number of hospital visits (adjusted odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02-1.16) and number of treating specialists (adjusted OR: 0.61; 95% CI: 0.45-0.83) were associated with PIMcog use. This study highlights a high-level use of medicines that can further impair cognition or reduce the effectiveness of CEIs in people with dementia. Efforts to improve quality use of medicines for this population are warranted.
    Matched MeSH terms: Cholinesterase Inhibitors/administration & dosage*; Cholinesterase Inhibitors/adverse effects
  4. Evaluation of neurotoxicity of repeated dermal application of chlorpyrifos on hippocampus of adult mice
    Mitra NK, Siong HH, Nadarajah VD
    Ann Agric Environ Med, 2008;15(2):211-6.
    PMID: 19061257
    Dermal absorption of chlorpyrifos, an organophosphate insecticide is important because of its use in agriculture and control of household pests. The objectives of this study are to investigate firstly, the biochemical changes in the blood and secondly, histomorphometric changes in the hippocampus of adult mice following dermal application of chlorpyrifos in sub-toxic doses. Male Swiss albino mice (60 days) were segregated into one control and two treated groups (n=10). Chlorpyrifos, diluted with xylene, was applied in doses of 1/2 of LD(50) (E1) and 1/5 of LD(50) (E2) over the tail of mice of the two treated groups, 6 hours daily for 3 weeks. AChE levels in the serum and brain were estimated using a spectrophotometric method (Amplex Red reagent). Coronal serial sections were stained with 0.2 % thionin in acetate buffer and pyramidal neurons of Cornu Ammonis of hippocampus were counted at 400x magnification using Image Pro Express software. At the end of 3 weeks, body weights were reduced significantly in E1 group. Serum AChE concentrations were reduced by 97 % in E1 and 74 % in E2 groups compared to controls. The neurons of CA 3 and CA 1 in the hippocampus showed evidences of morphological damage in both treated groups. Furthermore, the neuronal count was significantly reduced in CA 3 layer of hippocampus in E1 group.
    Matched MeSH terms: Cholinesterase Inhibitors/administration & dosage; Cholinesterase Inhibitors/pharmacokinetics; Cholinesterase Inhibitors/toxicity*
  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/chemical synthesis; Cholinesterase Inhibitors/pharmacology*; Cholinesterase Inhibitors/chemistry
  6. Probing simple structural modification of α-mangostin on its cholinesterase inhibition and cytotoxicity
    Khaw KY, Kumar P, Yusof SR, Ramanathan S, Murugaiyah V
    Arch Pharm (Weinheim), 2020 Nov;353(11):e2000156.
    PMID: 32716578 DOI: 10.1002/ardp.202000156
    α-Mangostin has been reported to possess a broad range of pharmacological effects including potent cholinesterase inhibition, but the development of α-mangostin as a potential lead compound is impeded by its toxicity. The present study investigated the impact of simple structural modification of α-mangostin on its cholinesterase inhibitory activities and toxicity toward neuroblastoma and liver cancer cells. The dialkylated derivatives retained good acetylcholinesterase (AChE) inhibitory activities with IC50 values between 4.15 and 6.73 µM, but not butyrylcholinesterase (BChE) inhibitory activities, compared with α-mangostin, a dual inhibitor (IC50 : AChE, 2.48 µM; BChE, 5.87 µM). Dialkylation of α-mangostin produced AChE selective inhibitors that formed hydrophobic interactions at the active site of AChE. Interestingly, all four dialkylated derivatives of α-mangostin showed much lower cytotoxicity, being 6.4- to 9.0-fold and 3.8- to 5.5-fold less toxic than their parent compound on neuroblastoma and liver cancer cells, respectively. Likewise, their selectivity index was higher by 1.9- to 4.4-fold; in particular, A2 and A4 showed improved selectivity index compared with α-mangostin. Taken together, modification of the hydroxyl groups of α-mangostin at positions C-3 and C-6 greatly influenced its BChE inhibitory and cytotoxic but not its AChE inhibitory activities. These dialkylated derivatives are viable candidates for further structural modification and refinement, worthy in the search of new AChE inhibitors with higher safety margins.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*; Cholinesterase Inhibitors/chemistry
  7. Synthesis of 2-(2-oxo-2H-chromen-4-yl)acetamides as potent acetylcholinesterase inhibitors and molecular insights into binding interactions
    Kara J, Suwanhom P, Wattanapiromsakul C, Nualnoi T, Puripattanavong J, Khongkow P, et al.
    Arch Pharm (Weinheim), 2019 Jul;352(7):e1800310.
    PMID: 31125474 DOI: 10.1002/ardp.201800310
    Sixteen novel coumarin-based compounds are reported as potent acetylcholinesterase (AChE) inhibitors. The most active compound in this series, 5a (IC50 0.04 ± 0.01 µM), noncompetitively inhibited AChE with a higher potency than tacrine and galantamine. Compounds 5d, 5j, and 5 m showed a moderate antilipid peroxidation activity. The compounds showed cytotoxicity in the same range as the standard drugs in HEK-293 cells. Molecular docking demonstrated that 5a acted as a dual binding site inhibitor. The coumarin moiety occupied the peripheral anionic site and showed π-π interaction with Trp278. The tertiary amino group displayed significant cation-π interaction with Phe329. The aromatic group showed π-π interaction with Trp83 at the catalytic anionic site. The long chain of methylene lay along the gorge interacting with Phe330 via hydrophobic interaction. Molecular docking was applied to postulate the selectivity toward AChE of 5a in comparison with donepezil and tacrine. Structural insights into the selectivity of the coumarin derivatives toward huAChE were explored by molecular docking and 3D QSAR and molecular dynamics simulation for 20 ns. ADMET analysis suggested that the 2-(2-oxo-2H-chromen-4-yl)acetamides showed a good pharmacokinetic profile and no hepatotoxicity. These coumarin derivatives showed high potential for further development as anti-Alzheimer agents.
    Matched MeSH terms: Cholinesterase Inhibitors/chemical synthesis; Cholinesterase Inhibitors/pharmacology*; Cholinesterase Inhibitors/chemistry
  8. Fulltext In vitro and ex-vivo cellular antioxidant protection and cognitive enhancing effects of an extract of Polygonum minus Huds (Lineminus™) demonstrated in a Barnes Maze animal model for memory and learning
    George A, Ng CP, O'Callaghan M, Jensen GS, Wong HJ
    BMC Complement Altern Med, 2014;14:161.
    PMID: 24886679 DOI: 10.1186/1472-6882-14-161
    Polygonum minus Huds.is a culinary flavouring that is common in South East Asian cuisine and as a remedy for diverse maladies ranging from indigestion to poor eyesight. The leaves of this herb have been reported to be high in antioxidants. Flavonoids which have been associated with memory, cognition and protection against neurodegeneration were found in P. minus.
    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
  9. Fulltext In-vitro and in-vivo validation of ethnopharmacological uses of methanol extract of Isodon rugosus Wall. ex Benth. (Lamiaceae)
    Janbaz KH, Arif J, Saqib F, Imran I, Ashraf M, Zia-Ul-Haq M, et al.
    BMC Complement Altern Med, 2014 Feb 22;14:71.
    PMID: 24559094 DOI: 10.1186/1472-6882-14-71
    BACKGROUND: Isodon rugosus is used in folk Pakistan traditional practices to cure ailments related to gastrointestinal, respiratory and cardiovascular problems. Present study was undertaken to validate these folkloric uses.

    METHODS: A crude methanol extract of the aerial parts of Isodon rugosus (Ir.Cr.) was used for both in vitro and in vivo experiments. The plant extract was tested on isolated rabbit jejunum preparations for possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. Acetylcholinesterase and butyrylcholinesterase inhibitory activities of Ir.Cr were also determined as well as its antioxidant activity. The in vivo antiemetic activity of the extract was evaluated by using the chick emesis model, while the analgesic and antipyretic activities were conducted on albino mice.

    RESULTS: The application of the crude extract of I. rugosus to isolated rabbit jejunum preparations exhibited relaxant effect (0.01-0.3 mg/ml). The Ir.Cr also relaxed K+(80 m M)-induced spastic contractions in isolated rabbit jejunum preparations and shifted the Ca+2 concentration response curves towards right (0.01-0.3 mg/ml). Similarly, the extract, when applied to the isolated rabbit tracheal preparations relaxed the carbachol (1 μM)--as well as K+ (80 mM)-induced contractions in a concentration range of 0.01-1.0 mg/ml. Moreover, it also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit aorta preparations. The Ir.Cr (80 mg/kg) demonstrated antipyretic activity on pyrogen-induced pyrexia in rabbits as compared to aspirin as standard drug. The Ir.Cr also exhibited anti-oxidant as well as inhibitory effect on acetyl- and butyryl-cholinesterase and lipoxygenase (0.5 mg/ml).

    CONCLUSIONS: The observed relaxant effect on isolated rabbit jejunum, trachea and aorta preparations caused by Ir.Cr is possibly to be mediated through Ca+2 channel blockade and therefore may provided scientific basis to validate the folkloric uses of the plant in the management of gastrointestinal, respiratory and cardiovascular ailments. The observed antioxidant activity as well as the lipoxygenase inhibitory activity may validate its traditional use in pain and inflammations.

    Matched MeSH terms: Cholinesterase Inhibitors/pharmacology; Cholinesterase Inhibitors/therapeutic use
  10. Fulltext Flaccid paralysis in an infant associated with a dirty wound and application of honey
    Joseph CJ, Khoo TB, Lee KY
    BMJ Case Rep, 2017 Jan 06;2017.
    PMID: 28062435 DOI: 10.1136/bcr-2016-218044
    An infant, who was born preterm at 36 weeks, presented with fever and ulcer at umbilical region which progressed to necrotising fasciitis of anterior abdominal wall. He was treated with intravenous penicillin, intravenous cloxacillin and local application of medicated honey. Subsequently, he required wound debridement. Postoperatively, he required prolonged invasive ventilation due to poor respiratory effort which was associated with hypotonia and areflexia. Nerve conduction study revealed absent responses. The diagnosis of infant botulism was made based on the clinical presentation, nerve conduction study and his clinical progress. Botulinum immunoglobulin was not available. He was treated with intravenous immunoglobulin and oral pyridostigmine. He was successfully extubated after 37 days, and currently the patient is doing well.
    Matched MeSH terms: Cholinesterase Inhibitors/therapeutic use*
  11. Fulltext "Why do I always see double?" A misdiagnosed case of ocular myasthenia gravis for 10 years
    Yousuf UA, Yashodhara BM, Thanigasalam T, Ting HS
    BMJ Case Rep, 2014 May 02;2014.
    PMID: 24792021 DOI: 10.1136/bcr-2013-203488
    A 58-year-old man presented with diplopia and partial ptosis for 10 years. It was non-progressive in nature, despite inadequate medical attention the patient received from non-specialists/general practitioners. He did not have fatigability or diurnal variation in weakness and was clinically stable without exacerbations of disease for a decade. He did not have features of Graves's disease, oculopharyngeal dystrophy, cranial nerve paralysis, polymyositis and stroke. The possibility of an atypical presentation of myasthenia gravis (MG) was considered and the patient was evaluated. Ice pack test was negative, Cogan's lid twitch (CLT) test was positive and high titres of acetylcholine receptor antibodies (AChR Ab) suggestive of MG were found. He was treated accordingly with a very good response.
    Matched MeSH terms: Cholinesterase Inhibitors/therapeutic use
  12. Fulltext An expedient synthesis, acetylcholinesterase inhibitory activity, and molecular modeling study of highly functionalized hexahydro-1,6-naphthyridines
    Almansour AI, Kumar RS, Arumugam N, Basiri A, Kia Y, Ali MA
    Biomed Res Int, 2015;2015:965987.
    PMID: 25710037 DOI: 10.1155/2015/965987
    A series of hexahydro-1,6-naphthyridines were synthesized in good yields by the reaction of 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones with cyanoacetamide in the presence of sodium ethoxide under simple mixing at ambient temperature for 6-10 minutes and were assayed for their acetylcholinesterase (AChE) inhibitory activity using colorimetric Ellman's method. Compound 4e with methoxy substituent at ortho-position of the phenyl rings displayed the maximum inhibitory activity with IC50 value of 2.12 μM. Molecular modeling simulation of 4e was performed using three-dimensional structure of Torpedo californica AChE (TcAChE) enzyme to disclose binding interaction and orientation of this molecule into the active site gorge of the receptor.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry*
  13. Fulltext The antiacetylcholinesterase and antileishmanial activities of Canarium patentinervium Miq
    Mogana R, Adhikari A, Debnath S, Hazra S, Hazra B, Teng-Jin K, et al.
    Biomed Res Int, 2014;2014:903529.
    PMID: 24949478 DOI: 10.1155/2014/903529
    In continuation of our natural and medicinal research programme on tropical rainforest plants, a bioassay guided fractionation of ethanolic extract of leaves of Canarium patentinervium Miq. (Burseraceae Kunth.) led to the isolation of scopoletin (1), scoparone (2), (+)-catechin (3), vomifoliol (4), lioxin (5), and syringic acid (6). All the compounds exhibited antiacetylcholinesterase activity with syringic acid, a phenolic acid exhibiting good AChE inhibition (IC50 29.53 ± 0.19 μ g/mL). All compounds displayed moderate antileishmanial activity with scopoletin having the highest antileishmanial activity (IC50 163.30 ± 0.32 μ g/mL). Given the aforementioned evidence, it is tempting to speculate that Canarium patentinervium Miq. represents an exciting scaffold from which to develop leads for treatment of neurodegenerative and parasitic diseases.
    Matched MeSH terms: Cholinesterase Inhibitors/chemistry
  14. Fulltext Phytochemicals content, antioxidant activity and acetylcholinesterase inhibition properties of indigenous Garcinia parvifolia fruit
    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*
  15. A molecular approach in drug development for Alzheimer's disease
    Agatonovic-Kustrin S, Kettle C, Morton DW
    Biomed Pharmacother, 2018 Oct;106:553-565.
    PMID: 29990843 DOI: 10.1016/j.biopha.2018.06.147
    An increase in dementia numbers and global trends in population aging across the world prompts the need for new medications to treat the complex biological dysfunctions, such as neurodegeneration associated with dementia. Alzheimer's disease (AD) is the most common form of dementia. Cholinergic signaling, which is important in cognition, is slowly lost in AD, so the first line therapy is to treat symptoms with acetylcholinesterase inhibitors to increase levels of acetylcholine. Out of five available FDA-approved AD medications, donepezil, galantamine and rivastigmine are cholinesterase inhibitors while memantine, a N-methyl d-aspartate (NMDA) receptor antagonist, blocks the effects of high glutamate levels. The fifth medication consists of a combination of donepezil and memantine. Although these medications can reduce and temporarily slow down the symptoms of AD, they cannot stop the damage to the brain from progressing. For a superior therapeutic effect, multi-target drugs are required. Thus, a Multi-Target-Directed Ligand (MTDL) strategy has received more attention by scientists who are attempting to develop hybrid molecules that simultaneously modulate multiple biological targets. This review highlights recent examples of the MTDL approach and fragment based strategy in the rational design of new potential AD medications.
    Matched MeSH terms: Cholinesterase Inhibitors/metabolism; Cholinesterase Inhibitors/pharmacology*; Cholinesterase Inhibitors/chemistry
  16. Fulltext Multi-targeting aurones with monoamine oxidase and amyloid-beta inhibitory activities: Structure-activity relationship and translating multi-potency to neuroprotection
    Liew KF, Lee EH, Chan KL, Lee CY
    Biomed Pharmacother, 2019 Feb;110:118-128.
    PMID: 30466001 DOI: 10.1016/j.biopha.2018.11.054
    Previously, a series of aurones bearing amine and carbamate functionalities was synthesized and evaluated for their cholinesterase inhibitory activity and drug-like attributes. In the present study, these aurones were evaluated for their multi-targeting properties in two Alzheimer's disease (AD)-related activities namely, monoamine oxidase (MAO) and amyloid-beta (Aβ) inhibition. Evaluation of the aurones for MAO inhibitory activity disclosed several potent selective inhibitors of MAO-B, particularly those with 6-methoxyl group attached at ring A. Of the different amine moieties attached as side chains, pyrrolidine-bearing aurones were prominent as represented by 2-2, the most potent inhibitor. Evaluation on the Aβ aggregation inhibition identified 4-3 as the best inhibitor with a percentage inhibition comparable to that of a known Aβ inhibitor curcumin. Examination on the neuroprotective ability of the more drug-like aurone 4-3 in two Caenorhabditis elegans neurodegeneration models showed 4-3 to protect the nematodes against both Aβ- and 6-hydroxydopamine-induced toxicities. These new activities further support 4-3 as a promising lead to develop the aurones as potential multipotent agents for neurodegenerative diseases.
    Matched MeSH terms: Cholinesterase Inhibitors/administration & dosage*; Cholinesterase Inhibitors/chemistry
  17. Ionic liquid mediated synthesis of mono- and bis-spirooxindole-hexahydropyrrolidines as cholinesterase inhibitors and their molecular docking studies
    Kia Y, Osman H, Kumar RS, Basiri A, Murugaiyah V
    Bioorg Med Chem, 2014 Feb 15;22(4):1318-28.
    PMID: 24461561 DOI: 10.1016/j.bmc.2014.01.002
    One pot, three-component reaction of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with isatin and sarcosine in molar ratios of 1:1:1 and 1:2:2 furnished to mono- and bis-spiropyrrolidine heterocyclic hybrids comprising functionalized piperidine, pyrrolidine and oxindole structural motifs. Both mono and bis-spiropyrrolidines displayed good inhibitory activity against acetylcholinesterase (AChE) with IC₅₀ values of 2.36-9.43 μM. For butyrylcholinesterase (BChE), mono-cycloadducts in series 8 with IC₅₀ values of lower than 10 μM displayed better inhibitory activities than their bis-cycloadduct analogs in series 9 with IC₅₀ values of 7.44-19.12 μM. The cycloadducts 9j and 8e were found to be the most potent AChE and BChE inhibitors with IC₅₀ values of 2.35 and 3.21 μM, respectively. Compound 9j was found to be competitive inhibitor of AChE while compound 8e was a mixed-mode inhibitor of BChE with calculated Ki values of 2.01 and 6.76 μM, respectively. Molecular docking on Torpedo californica AChE and human BChE showed good correlation between IC₅₀ values and free binding energy values of the synthesized compounds docked into the active site of the enzymes.
    Matched MeSH terms: Cholinesterase Inhibitors/chemical synthesis*; Cholinesterase Inhibitors/metabolism; 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/chemical synthesis; Cholinesterase Inhibitors/pharmacology*; Cholinesterase Inhibitors/chemistry*
  19. Microwave assisted synthesis, cholinesterase enzymes inhibitory activities and molecular docking studies of new pyridopyrimidine derivatives
    Basiri A, Murugaiyah V, Osman H, Kumar RS, Kia Y, Ali MA
    Bioorg Med Chem, 2013 Jun 1;21(11):3022-31.
    PMID: 23602518 DOI: 10.1016/j.bmc.2013.03.058
    A series of hitherto unreported pyrido-pyrimidine-2-ones/pyrimidine-2-thiones were synthesized under microwave assisted solvent free reaction conditions in excellent yields and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activity. Among the pyridopyrimidine derivatives, 7e and 7l displayed 2.5- and 1.5-fold higher enzyme inhibitory activities against AChE as compared to standard drug, galanthamine, with IC50 of 0.80 and 1.37 μM, respectively. Interestingly, all the compounds except 6k, 7j and 7k displayed higher inhibitory potential against BChE enzyme in comparison to standard with IC50 ranging from 1.18 to 18.90 μM. Molecular modeling simulations of 7e and 7l was performed using three-dimensional structure of Torpedo californica AChE (TcAChE) and human butyrylcholinesterase (hBChE) enzymes to disclose binding interaction and orientation of these molecule into the active site gorge of respective receptors.
    Matched MeSH terms: Cholinesterase Inhibitors/chemical synthesis*; Cholinesterase Inhibitors/chemistry
  20. 4-Phenylcoumarins from Mesua elegans with acetylcholinesterase inhibitory activity
    Awang K, Chan G, Litaudon M, Ismail NH, Martin MT, Gueritte F
    Bioorg Med Chem, 2010 Nov 15;18(22):7873-7.
    PMID: 20943395 DOI: 10.1016/j.bmc.2010.09.044
    A significant acetylcholinesterase (AChE) inhibitory activity was observed for the hexane extract from the bark of Mesua elegans (Clusiaceae). Thus, the hexane extract was subjected to chemical investigation, which led to the isolation of nine 4-phenylcoumarins, in which three are new; mesuagenin A (1), mesuagenin C (3), mesuagenin D (4) and one new natural product; mesuagenin B (2). The structures of the isolated compounds were characterized by spectroscopic data interpretation, especially 1D and 2D NMR. Four compounds showed significant AChE inhibitory activity, with mesuagenin B (2) being the most potent (IC(50)=0.7μM).
    Matched MeSH terms: Cholinesterase Inhibitors/isolation & purification; Cholinesterase Inhibitors/pharmacology; Cholinesterase Inhibitors/chemistry*
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