P491, I Trionfi / Petrarca. Image 078

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Evaluation of Activity of Some 2,5-Disubstituted Benzoxazole Derivatives against Acetylcholinesterase, Butyrylcholinesterase and Tyrosinase: ADME Prediction, DFT and Comparative Molecular Docking Studies

In this study, p-tert-butyl at position 2 and acetamide bridged 4-substituted piperazine/piperidine at position 5 bearing benzoxazole derivatives were evaluated for their in vitro inhibitory activity against AChE, BChE and Tyrosinase, which are important targets in reducing the adverse effects of Alzheimer's disease. The most active 1 g inhibited the BChE at a concentration of 50 mu M by 54 +/- 0.75%. Molecular docking studies of the compounds against BChE (PDB: 4BDS) were performed with Schrodinger and AutoDock Vina and the results were compared. Schrodinger docking scores were found to be more consistent. Estimated ADME profiles and bioactivity scores of the compounds were calculated and found to be compatible with Lipinski and other limiting rules. Geometric optimization parameters, MEP analysis and HUMO and LUMO quantum parameters of the most active 1 g were calculated by using DFT/B3LYP theory and 6-311 G (d,p) base set and results was viewed

Survey of 55 Turkish Salvia taxa for their acetylcholinesterase inhibitory and antioxidant activities

In the current work, our target was to screen inhibitory potentials of 55 Turkish Salvia taxa, 28 of which are endemic, against acetylcholinesterase (AChE), which is a chief enzyme in pathogenesis of Alzheimer's disease (AD). The dichloromethane, ethyl acetate, and methanol extracts prepared from 55 Salvia taxa were tested for their AChE inhibitory activity at 25, 50, and 100 mu g/ml using an ELISA microplate reader. The extracts were also screened for their scavenging effect against DPPH radical and iron-chelating capacity. Total phenol and total flavonoid contents of Salvia fruticosa were determined. Among the 165 Salvia extracts screened, only the dichloromethane extract of S. fruticosa showed inhibition towards AChE at 100 mu g/ml having 51.07% of inhibition, while only the dichloromethane and ethyl acetate extracts of Salvia cilicica had a notable iron-chelating capacity at 100 mu g/ml having 54.71% of chelating capacity. Most of the extracts showed remarkable scavenging effect against DPPH radical

Assessment Of Anticholinesterase And Antioxidant Properties Of Selected Sage (Salvia) Species With Their Total Phenol And Flavonoid Contents

In this study, cholinesterase inhibitory potential relevant to Alzheimer's disease and antioxidant activities of the dichloromethane, ethyl acetate, and ethanol extracts from the aerial parts and/or roots of fourteen Salvia (sage) species (S. argentea, S. bracteata, S. caespitosa, S. cryptantha, S. glutinosa, S. indica, S. microstegia, S. multicaulis, S. pinnata, S. quezelii, S. syriaca, S. tobeyi, S. verticillata subsp. amasiaca, and S. viscosa) were investigated. Cholinesterase inhibition was determined by Ellman method at 25, 50, and 100?gml -1. Their antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, metal-chelation capacity, and ferric-reducing antioxidant power (FRAP) assays. Total phenol and flavonoid contents of the extracts were also determined. The dichloromethane and ethanol extracts of the aerial parts of S. cryptantha were the most active ones against AChE (56.22±1.07%) and BChE (33.80±4.18%), respectively. The ethanol extracts exhibited better scavenging activity and FRAP. Anticholinesterase activity of 9 Salvia species (S. argentea, S. bracteata, S. caespitosa, S. indica, S. pinnata, S. quezelii, S. syriaca, S. tobeyi, and S. viscosa) is reported for the first time in the current study. © 2012 Elsevier B.V.TUBITAK-TBAG-104T450F.S. Senol expresses her genuine gratitude to the Scientific and Technological Research Council of Turkey (TUBITAK) for the scholarship provided for her Ph.D. program. Financial support for the field trips provided by Scientific and Technical Research Council of Turkey ( TUBITAK-TBAG-104T450 ) is also greatly acknowledged

Butyrylcholinesterase-inhibiting natural coumarin molecules as potential leads

Seventeen natural coumarin derivatives; badrakemin (1), 14′-acetoxybadrakemin (2), badrakemone (3), 14′-acetoxybadrakemone (4), colladonin (5), colladonin acetate (6), 14′-acetoxycolladonin (7), karatavicinol (8), deltoin (9), smyrnioridin (10), marmesin (11), osthol (12), oxypeucedanin (13), oxypeucedanin hydrate (14), isoimperatorin (15), scopoletin (16), and umbelliprenin (17), were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the sister enzymes that play a critical role in the pathology of Alzheimer's disease as well as tyrosinase (TYR) as the target for Parkinson's disease. The tested coumarins were more selective against BChE, where the coumarins 2, 5, 8, and 15 (IC50 = 30.3 μM, 29.2 μM, 37.2 μM, and 50.1 μM, respectively) displayed higher BChE inhibition than the reference (galanthamine, IC50 = 60.2 μM) at 100 μg/mL. Only four coumarins (2, 5, 9, and 15) showed inhibition against AChE. Binding conformations of the coumarins (2, 5, 8, 9, and 15) within the active sites of AChE and BChE were explored via molecular docking experiments. The docked compounds were oriented by the interactions with the oxyanion hole and the peripheral anionic site residues of AChE/BChE. The coumarin derivatives 1–17 was found to have no or low inhibition (2.03 ± 0.92 %–12.91 ± 0.40 %) against TYR at 100 μg/mL. Our findings revealed that coumarins could be promising lead compounds for designing novel anti-Alzheimer drug candidates

Anticholinesterase, Antioxidant, Analgesic and Anti-Inflammatory Activity Assessment of Xeranthemum Annuum L. And Isolation of Two Cyanogenic Compounds

Context:Xeranthemum annuum L. (Asteraceae) (XA) is an ornamental and medicinal species with limited bioactivity and phytochemical data.Objective: Identification of anticholinesterase, antioxidant, anti-inflammatory and analgesic effects of the flower and root-stem (R-S) extracts of XA.Materials and methods: Anticholinesterase (at 100gmL(-1)) and antioxidant (at 1000gmL(-1)) effects of various extracts were evaluated via microtiter assays, while anti-inflammatory and analgesic effects of the R-S extracts were tested using carrageenan-induced hind paw oedema (100 and 200mg kg(-1)) and p-benzoquinone (PBQ) writhing models (200mg kg(-1)) in male Swiss albino mice. The R-S ethanol extract of XA was subjected to isolation studies using conventional chromatographic methods.Results: Most of the extracts showed inhibition over 85% against butyrylcholinesterase and no inhibition towards acetylcholinesterase. The flower chloroform and the R-S ethyl acetate extracts were most effective (97.850.94% and 96.89 +/- 1.09%, respectively). The R-S ethanol extract displayed a remarkable scavenging activity against DPPH (77.33 +/- 1.99%) and in FRAP assay, while the hexane extract of the R-S parts possessed the highest metal-chelating capacity (72.79 +/- 0.33%). The chloroform extract of the R-S caused a significant analgesic effect (24.4%) in PBQ writhing model. No anti-inflammatory effect was observed. Isolation of zierin and zierin xyloside, which were inactive in anticholinesterase assays, was achieved from the R-S ethanol extract.Discussion and conclusion: This is the first report of anticholinesterase, antioxidant, analgesic and anti-inflammatory activities and isolation of zierin and zierin xyloside from XA. Therefore, XA seems to contain antioxidant and BChE-inhibiting compounds.Wo

Butyrylcholinesterase-inhibiting natural coumarin molecules as potential leads

Seventeen natural coumarin derivatives; badrakemin (1), 14′-acetoxybadrakemin (2), badrakemone (3), 14′-acetoxybadrakemone (4), colladonin (5), colladonin acetate (6), 14′-acetoxycolladonin (7), karatavicinol (8), deltoin (9), smyrnioridin (10), marmesin (11), osthol (12), oxypeucedanin (13), oxypeucedanin hydrate (14), isoimperatorin (15), scopoletin (16), and umbelliprenin (17), were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the sister enzymes that play a critical role in the pathology of Alzheimer’s disease as well as tyrosinase (TYR) as the target for Parkinson’s disease. The tested coumarins were more selective against BChE, where the coumarins 2, 5, 8, and 15 (IC50 = 30.3 μM, 29.2 μM, 37.2 μM, and 50.1 μM, respectively) displayed higher BChE inhibition than the reference (galanthamine, IC50 = 60.2 μM) at 100 μg/mL. Only four coumarins (2, 5, 9, and 15) showed inhibition against AChE. Binding conformations of the coumarins (2, 5, 8, 9, and 15) within the active sites of AChE and BChE were explored via molecular docking experiments. The docked compounds were oriented by the interactions with the oxyanion hole and the peripheral anionic site residues of AChE/BChE. The coumarin derivatives 1–17 was found to have no or low inhibition (2.03 ± 0.92 %–12.91 ± 0.40 %) against TYR at 100 μg/mL. Our findings revealed that coumarins could be promising lead compounds for designing novel anti-Alzheimer drug candidates