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Fulltext Volatile profiling of aromatic traditional medicinal plant, Polygonum minus in different tissues and its biological activities

Ahmad R, Baharum SN, Bunawan H, Lee M, Mohd Noor N, Rohani ER, et al.

Molecules, 2014 Nov 20;19(11):19220-42.
PMID: 25420073 DOI: 10.3390/molecules191119220

The aim of this research was to identify the volatile metabolites produced in different organs (leaves, stem and roots) of Polygonum minus, an important essential oil producing crop in Malaysia. Two methods of extraction have been applied: Solid Phase Microextraction (SPME) and hydrodistillation coupled with Gas Chromatography-Mass Spectrometry (GC-MS). Approximately, 77 metabolites have been identified and aliphatic compounds contribute significantly towards the aroma and flavour of this plant. Two main aliphatic compounds: decanal and dodecanal were found to be the major contributor. Terpenoid metabolites were identified abundantly in leaves but not in the stem and root of this plant. Further studies on antioxidant, total phenolic content, anticholinesterase and antimicrobial activities were determined in the essential oil and five different extracts. The plant showed the highest DPPH radical scavenging activity in polar (ethanol) extract for all the tissues tested. For anti-acetylcholinesterase activity, leaf in aqueous extract and methanol extract showed the best acetylcholinesterase inhibitory activities. However, in microbial activity, the non-polar extracts (n-hexane) showed high antimicrobial activity against Methicillin-resistant Staphylococcus aureus (MRSA) compared to polar extracts. This study could provide the first step in the phytochemical profiles of volatile compounds and explore the additional value of pharmacology properties of this essential oil producing crop Polygonum minus.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology
Fulltext Synthesis of Benzimidazole-Based Analogs as Anti Alzheimer's Disease Compounds and Their Molecular Docking Studies

Adalat B, Rahim F, Taha M, Alshamrani FJ, Anouar EH, Uddin N, et al.

Molecules, 2020 Oct 20;25(20).
PMID: 33092223 DOI: 10.3390/molecules25204828

We synthesized 10 analogs of benzimidazole-based thiosemicarbazide 1 (a-j) and 13 benzimidazole-based Schiff bases 2 (a-m), and characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibition activities. All the synthesized analogs showed varying degrees of acetylcholinesterase and butyrylcholinesterase inhibitory potentials in comparison to the standard drug (IC50 = 0.016 and 4.5 µM. Amongst these analogs 1 (a-j), compounds 1b, 1c, and 1g having IC50 values 1.30, 0.60, and 2.40 µM, respectively, showed good acetylcholinesterase inhibition when compared with the standard. These compounds also showed moderate butyrylcholinesterase inhibition having IC50 values of 2.40, 1.50, and 2.40 µM, respectively. The rest of the compounds of this series also showed moderate to weak inhibition. While amongst the second series of analogs 2 (a-m), compounds 2c, 2e, and 2h having IC50 values of 1.50, 0.60, and 0.90 µM, respectively, showed moderate acetylcholinesterase inhibition when compared to donepezil. Structure Aactivity Relation of both synthesized series has been carried out. The binding interactions between the synthesized analogs and the enzymes were identified through molecular docking simulations.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
Synthesis, Molecular Docking, and Biological Evaluation of Benzimidazole Derivatives as Selective Butyrylcholinesterase Inhibitors

Ha ZY, Ong HC, Oo CW, Yeong KY

Curr Alzheimer Res, 2020;17(13):1177-1185.
PMID: 33602088 DOI: 10.2174/1567205018666210218151228

BACKGROUND: Benzimidazole is an interesting pharmacophore which has been extensively studied in medicinal chemistry due to its high affinity towards various enzymes and receptors. Its derivatives have been previously shown to possess a wide range of biological activities including anthelmintic, antihypertensive, antiulcer, as well as anticholinesterase activity.
OBJECTIVE: The objective of this study is to search for more potent benzimidazole-based cholinesterase inhibitors, through the modification of the 1- and 2-positions of the benzimidazole core.
METHODS: Synthesis of compounds were carried out via a 4-step reaction scheme following a previously reported protocol. Structure-activity relationship of the compounds are established through in vitro cholinesterase assays and in silico docking studies. Furthermore, cytotoxicity and blood brain barrier (BBB) permeability of the compounds were also investigated.
RESULTS: Among the synthesised compounds, three of them (5IIa, 5IIb, and 5IIc) exhibited potent selective butyrylcholinesterase inhibition at low micromolar level. The compounds did not show any significant cytotoxicity when tested against a panel of human cell lines. Moreover, the most active compound, 5IIc, was highly permeable across the blood brain barrier.
CONCLUSION: In total 10 benzimidazole derivatives were synthesized and screened for their AChE and BuChE inhibitory activities. Lead compound 5Iic, represents a valuable compound for further development as potential AD therapeutics.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
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/pharmacology*
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*
Fulltext Antioxidant, Anti-Inflammatory, and Inhibition of Acetylcholinesterase Potentials of Cassia timoriensis DC. Flowers

Alhawarri MB, Dianita R, Razak KNA, Mohamad S, Nogawa T, Wahab HA

Molecules, 2021 Apr 29;26(9).
PMID: 33946788 DOI: 10.3390/molecules26092594

Despite being widely used traditionally as a general tonic, especially in South East Asia, scientific research on Cassia timoriensis, remains scarce. In this study, the aim was to evaluate the in vitro activities for acetylcholinesterase (AChE) inhibitory potential, radical scavenging ability, and the anti-inflammatory properties of different extracts of C. timoriensis flowers using Ellman's assay, a DPPH assay, and an albumin denaturation assay, respectively. With the exception of the acetylcholinesterase activity, to the best of our knowledge, these activities were reported for the first time for C. timoriensis flowers. The phytochemical analysis confirmed the existence of tannins, flavonoids, saponins, terpenoids, and steroids in the C. timoriensis flower extracts. The ethyl acetate extract possessed the highest phenolic and flavonoid contents (527.43 ± 5.83 mg GAE/g DW and 851.83 ± 10.08 mg QE/g DW, respectively) as compared to the other extracts. In addition, the ethyl acetate and methanol extracts exhibited the highest antioxidant (IC50 20.12 ± 0.12 and 34.48 ± 0.07 µg/mL, respectively), anti-inflammatory (92.50 ± 1.38 and 92.22 ± 1.09, respectively), and anti-AChE (IC50 6.91 ± 0.38 and 6.40 ± 0.27 µg/mL, respectively) activities. These results suggest that ethyl acetate and methanol extracts may contain bioactive compounds that can control neurodegenerative disorders, including Alzheimer's disease, through high antioxidant, anti-inflammatory, and anti-AChE activities.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
A new sesquiterpenoid from the rhizomes of Homalomena sagittifolia

Wong KC, Hamid A, Eldeen IM, Asmawi MZ, Baharuddin S, Abdillahi HS, et al.

Nat Prod Res, 2012;26(9):850-8.
PMID: 21999629 DOI: 10.1080/14786419.2010.551770

A new sesquiterpenoid, 1α,4β,7β-eudesmanetriol (1), was isolated together with the known compounds 1β,4β,7β-eudesmanetriol (2) and oplopanone (3) from the rhizomes of Homalomena sagittifolia. The structures of these compounds were determined by extensive spectral analyses. The compounds 1 and 2 inhibited growth of Pseudomonas stutzeri with a MIC value of 117 µM when evaluated for antibacterial activity using the minimum concentration assay. Both these compounds showed remarkable activities against acetylcholinesterase enzyme with IC(50) values ranging between 25 and 26 µM. The isolation of these sesquiterpenoids and their biological activities observed in this study support the reported traditional uses of H. sagittifolia for the treatment of microbial related diseases and central nervous system disorders.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology
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/pharmacology*
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/pharmacology*
Prediction of Anti-Alzheimer's Activity of Flavonoids Targeting Acetylcholinesterase in silico

Das S, Laskar MA, Sarker SD, Choudhury MD, Choudhury PR, Mitra A, et al.

Phytochem Anal, 2017 Jul;28(4):324-331.
PMID: 28168765 DOI: 10.1002/pca.2679

INTRODUCTION: Prenylated and pyrano-flavonoids of the genus Artocarpus J. R. Forster & G. Forster are well known for their acetylcholinesterase (AChE) inhibitory, anti-cholinergic, anti-inflammatory, anti-microbial, anti-oxidant, anti-proliferative and tyrosinase inhibitory activities. Some of these compounds have also been shown to be effective against Alzheimer's disease.
OBJECTIVE: The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease.
METHODOLOGY: Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and quantitative structure-activity relationship (QSAR) were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman's method.
RESULTS: In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AChE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative compound 20 was the best scorer, i.e. -31.6392 and IC50 was predicted as 6.025 nM.
CONCLUSION: Results indicated that flavonoids could be efficient inhibitors of AChE and thus, could be useful in the management of Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
Tyrosinase inhibition, anti-acetylcholinesterase, and antimicrobial activities of the phytochemicals from Gynotroches axillaris Blume

Abed SA, Sirat HM, Taher M

Pak J Pharm Sci, 2016 Nov;29(6):2071-2078.
PMID: 28375126

The leaves of Gynotroches axillaris were chemically and biologically studied. Sequential extraction of the leaves using petroleum ether, chloroform, and methanol afforded three extracts. Purification of pet. ether extract yielded, squalene and β-amyrin palmitate as the major compounds, together with palmitic acid and myristic acid as the minor components. The methanol extract yielded two flavonoids, quercitrin and epicatechin. The isolated compounds were characterized by MS, IR and NMR (1D and 2D). Anti-acetyl cholinesterase screening using TLC bio-autography assay showed that palmitic acid and myristic acid were the strongest inhibition with detection limit 1.14 and 1.28 μ/g/ 5 μL respectively. Antibacterial against Gram-positive and negative and antifungal activities exhibited that β-amyrin palmitate was the strongest (450-225 μ/mL) against all the tested microbes. The tyrosinase inhibition assay of extracts and the pure compounds were screened against tyrosinase enzyme. The inhibition percentage (I%) of methanol extract against tyrosinase enzyme was stronger than the other extracts with value 68.4%. Quercitrin (59%) was found to be the highest in the tyrosinase inhibition activity amongst the pure compounds. To the best of our knowledge, this is first report on the phytochemicals, tyrosinase inhibition, anti-acetycholinesterase and antimicrobial activities of the leaves of G. axillaris.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
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/pharmacology*
AChE inhibitor: a regio- and stereo-selective 1,3-dipolar cycloaddition for the synthesis of novel substituted 5,6-dimethoxy spiro[5.3']-oxindole-spiro-[6.3″]-2,3-dihydro-1H-inden-1″-one-7-(substituted aryl)-tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole

Ashraf Ali M, Ismail R, Choon TS, Kumar RS, Osman H, Arumugam N, et al.

Bioorg Med Chem Lett, 2012 Jan 1;22(1):508-11.
PMID: 22142546 DOI: 10.1016/j.bmcl.2011.10.087

Pyrrolothiazolyloxindole analogues share vital pharmacological properties, considered useful in Alzheimer's disease (AD). The aim of this study was synthesis and evaluate pyralothiazolyloxindole analogues if possess acetyl cholinesterase (AChE) inhibitory activity. The easily accessible one-pot synthesis of these compounds resulted to be significantly less difficult and expensive than that of donepezil. Several compounds possess anti-cholinesterase activity in the order of micro and sub-micromolar. Particularly, compound was the most potent inhibitors of the series against acetyl cholinesterase enzyme with IC(50) 0.11μmol/L.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
Conventional versus microwave assisted synthesis, molecular docking and enzyme inhibitory activities of new 3,4,5-trisubstituted-1,2,4-triazole analogues

Virk NA, Rehman A, Abbasi MA, Siddiqui SZ, Rashid U, Iqbal J, et al.

Pak J Pharm Sci, 2018 Jul;31(4(Supplementary)):1501-1510.
PMID: 30058542

N-(Substituted)-5-(1-(4-methoxyphenylsulfonyl)piperidin-4-yl)-4H-1,2,4-triazol-3-ylthio) acetamide were synthesized by following conventional as well as microwave assisted protocol through five consecutive steps under the impact of various reaction conditions to control the reaction time and the yield of product. Starting from 4-methoxybenzenesulfonyl chloride and ethyl isonipecotate, product 3 was obtained which was converted into product 4 by treating with hydrazine hydrate. In step 3, the product 4 was refluxed with methyl isothiocyanate and KOH to yield compound 5 which was finally treated with variety of N-substituted acetamides to yield an array of different new compounds (8a-k). These synthesized compounds were evaluated for their inhibition potential against bovine carbonic anhydrase (bCA-II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Compound 8g demonstrated good activity against bCA-II, AChE and BChE with IC50 values of 8.69 ± 0.38 μM, 11.87±0.19 μM and 26.01±0.55 μM respectively. SAR studies assisted with molecular docking were carried out to explore the mode of binding of the compounds against the studied enzymes.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology
BSA Binding, molecular docking and in vitro biological screening of some new 1, 2, 4-triazole heterocycles bearing azinane nucleus

Iqbal J, Rehman A, Abbasi MA, Siddiqui SZ, Khalid H, Laulloo SJ, et al.

Pak J Pharm Sci, 2020 Jan;33(1):149-160.
PMID: 32122843

A series of new compounds (5a-q), derived from 5-(1-(4-nitrophenylsulfonyl) piperidin-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol (3) were proficiently synthesized to evaluate their biological activities. 1-(4-Nitrophenylsulfonyl) piperidine-4-carbohydrazide (2) was refluxed with phenylisothiocyanate to yield an adduct which was cyclized to compound 3 by reflux reaction with 10 % potassium hydroxide. The targeted compounds 5a-q, were synthesized by stirring alkyl/aralkyl halides (4a-q) and compound 3 in a polar aprotic solvent. 1H-NMR, 13C-NMR, EI-MS and IR spectral techniques were employed to confirm the structures of all the synthesized compounds. The compounds were biologically evaluated for BSA binding studies followed by anti-bacterial, anti-inflammatory and acetylcholinesterase (AChE) activities. The active sites responsible for the best AChE inhibition were identified through molecular docking studies. Compound 5e bearing 4-chlorobenzyl moiety found most active antibacterial and anti-inflammatory agent among the synthesized compounds. The whole library of synthesized compounds except compounds 5d and 5f was found highly active for AChE inhibition and recommended for in vivo studies so that their therapeutic applications may come in utilization.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
Phytochemicals from Dodonaea viscosa and their antioxidant and anticholinesterase activities with structure-activity relationships

Muhammad A, Tel-Çayan G, Öztürk M, Duru ME, Nadeem S, Anis I, et al.

Pharm Biol, 2016 Sep;54(9):1649-55.
PMID: 26866457 DOI: 10.3109/13880209.2015.1113992

Context Dodonaea viscosa (L.) Jacq (Sapindaceae) has been used in traditional medicine as antimalarial, antidiabetic and antibacterial agent, but further investigations are needed. Objective This study determines the antioxidant and anticholinesterase activities of six compounds (1-6) and two crystals (1A and 3A) isolated from D. viscosa, and discusses their structure-activity relationships. Materials and methods Antioxidant activity was evaluated using six complementary tests, i.e., β-carotene-linoleic acid; DPPH(•), ABTS(•+), superoxide scavenging, CUPRAC and metal chelating assays. Anticholinesterase activity was performed using the Elman method. Results Clerodane diterpenoids (1 and 2) and phenolics (3-6) - together with three crystals (1A, 3A and 7A) - were isolated from the aerial parts of D. viscosa. Compound 3A exhibited good antioxidant activity in DPPH (IC50: 27.44 ± 1.06 μM), superoxide (28.18 ± 1.35% inhibition at 100 μM) and CUPRAC (A0.5: 35.89 ± 0.09 μM) assays. Compound 5 (IC50: 11.02 ± 0.02 μM) indicated best activity in ABTS assay, and 6 (IC50: 14.30 ± 0.18 μM) in β-carotene-linoleic acid assay. Compounds 1 and 3 were also obtained in the crystal (1A and 3A) form. Both crystals showed antioxidant activity. Furthermore, crystal 3A was more active than 3 in all activity tests. Phenol 6 possessed moderate anticholinesterase activity against acetylcholinesterase and butyrylcholinesterase enzymes (IC50 values: 158.14 ± 1.65 and 111.60 ± 1.28 μM, respectively). Discussion and conclusion This is the first report on antioxidant and anticholinesterase activities of compounds 1, 2, 5, 6, 1A and 3A, and characterisation of 7A using XRD. Furthermore, the structure-activity relationships are also discussed in detail for the first time.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
Chemical profile and antiacetylcholinesterase, antityrosinase, antioxidant and α-glucosidase inhibitory activity of Cynometra cauliflora L. leaves

Ado MA, Abas F, Ismail IS, Ghazali HM, Shaari K

J Sci Food Agric, 2015 Feb;95(3):635-42.
PMID: 25048579 DOI: 10.1002/jsfa.6832

The aim of the current study was (i) to evaluate the bioactive potential of the leaf methanolic extract of Cynometra cauliflora L., along with its respective hexane, dichloromethane, ethyl acetate (EtOAc), n-butanol (n-BuOH) and aqueous fractions, in inhibiting the enzymes α-glucosidase, acetylcholinesterase (AChE) and tyrosinase as well as evaluating their antioxidant activities. (ii) In addition, in view of the limited published information regarding the metabolite profile of C. cauliflora, we further characterized the profiles of the EtOAc and n-BuOH fractions using liquid chromatography-diode array detection-electrospray ionization-tandem mass spectrometry.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology
2-Furoic piperazide derivatives as promising drug candidates of type 2 diabetes and Alzheimer's diseases: In vitro and in silico studies

Abbasi MA, Hassan M, Ur-Rehman A, Siddiqui SZ, Hussain G, Shah SAA, et al.

Comput Biol Chem, 2018 Dec;77:72-86.
PMID: 30245349 DOI: 10.1016/j.compbiolchem.2018.09.007

The heterocyclic compounds have been extensively reported for their bioactivity potential. The current research work reports the synthesis of some new multi-functional derivatives of 2-furoic piperazide (1; 1-(2-furoyl)piperazine). The synthesis was initiated by reacting the starting compound 1 with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (2) in a basic, polar and protic medium to obtain the parent sulfonamide 3 which was then treated with different electrophiles, 4a-g, in a polar and aprotic medium to acquire the designed molecules, 5a-g. These convergent derivatives were evaluated for their inhibitory potential against α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Acarbose was used as a reference standard for α-glucosidase inhibition while eserine for AChE and BChE inhibition. Some of the synthesized compounds were identified as promising inhibitors of these three enzymes and their bioactivity potentials were also supported by molecular docking study. The most active compounds among the synthetic analogues might be helpful in drug discovery and development for the treatment of type 2 diabetes and Alzhiemer's diseases.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
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/pharmacology*
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/pharmacology*

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