Synthesis and bioactivity of novel C2-glycosyl triazole derivatives as acetylcholinesterase inhibitors

AbstractNew C2-glycosyl triazole derivatives 6a–l were synthesized by cyclization of glycosyl acylthiosemicarbazides 5 in refluxing 3 N sodium hydroxide aqueous solution. Substrates 5 were obtained by the reaction of glycosyl isothiocyanate 3 with various hydrazides. The acetylcholinesterase (AChE) inhibitory activities of compounds 6 were tested by Ellman’s method. Compounds that exhibited over 85% inhibition were subsequently evaluated for the IC50 values. Compound 6f possesses the best acetylcholinesterase-inhibition activity with IC50 of 1.46±0.25 μg/mL.

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Synthesis and bioactivity of novel C2-glycosyl benzofuranylthiazoles derivatives as acetylcholinesterase inhibitors

Journal of Chemical Research ◽

10.1177/1747519819856973 ◽

2019 ◽

Vol 43 (7-8) ◽

pp. 257-261

Author(s):

Lei Wang ◽

Yu-Ran Wu ◽

Shu-Ting Ren ◽

Long Yin ◽

You-Xian Wang ◽

...

Keyword(s):

Inhibitory Concentration ◽

Acetylcholinesterase Inhibitors ◽

Acetylcholinesterase Inhibition ◽

Inhibition Activity ◽

Active Compounds ◽

Inhibitory Activities ◽

Ellman’S Method

A new series of C2-glycosyl benzofuranylthiazole derivatives was synthesised by the further cyclization of glycosyl thiourea and 2-(bromoacetyl)-benzofuran via Hantzsch’s method. The corresponding 2-(bromoacetyl)-benzofuran derivatives were obtained by the reaction from various salicylaldehydes, and the glycosyl thiourea was prepared through a series of steps from D-Glucosamine. The acetylcholinesterase-inhibitory activities of the products were tested by Ellman’s method. The most active compounds were subsequently evaluated for the 50% inhibitory concentration values. N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-4-(5-methoxy-benzofuran-2-yl)-1,3-thiazole-2-amine possessed the best acetylcholinesterase-inhibition activity with a 50% inhibitory concentration of 2.03 ± 0.26 μM.

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Synthesis and bioactivity of novel C2-glycosyl oxadiazole derivatives as acetylcholinesterase inhibitors

Heterocyclic Communications ◽

10.1515/hc-2018-0166 ◽

2018 ◽

Vol 24 (6) ◽

pp. 333-338 ◽

Cited By ~ 2

Author(s):

Lei Wang ◽

Yu-Ran Wu ◽

Shu-Ting Ren ◽

Long Yin ◽

Xiu-Jian Liu ◽

...

Keyword(s):

Inhibitory Concentration ◽

Acetylcholinesterase Inhibitors ◽

Inhibition Activity ◽

Ache Inhibition ◽

Active Compounds ◽

Oxadiazole Derivatives ◽

Inhibitory Activities ◽

Ellman’S Method

Abstract A series of glycosyl-substituted 1,3,4-oxadiazoles were synthesized by cyclization of glycosyl-acylthiosemicarbazides via a base-catalyzed reaction. The starting glycosyl-acylthiosemicarbazide derivatives were obtained by the reaction of glycosyl isothiocyanate with various hydrazides. The acetylcholinesterase (AChE) inhibitory activities of the products were tested by Ellman’s method. The most active compounds were subsequently evaluated for the 50% inhibitory concentration (IC50) values. N-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranosyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole-2-amine (6i) possesses the best AChE -inhibition activity with an IC50 of 1.61±0.34 μm.

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Phytochemical Constituents and Cholinesterase Inhibitory Activities of Millingtonia hortensis

Walailak Journal of Science and Technology (WJST) ◽

10.48048/wjst.2018.4597 ◽

2017 ◽

Vol 15 (8) ◽

pp. 589-597

Author(s):

Warachate KHOBJAI ◽

Orapit SUTHIVATTANAKUL ◽

Somsiri PANUWATTANAWONG

Keyword(s):

Ache Activity ◽

Leaf Extract ◽

Acetylcholinesterase Inhibitors ◽

Gas Chromatography Mass Spectrometry ◽

Enzyme Analysis ◽

Leaf Extracts ◽

Cholinesterase Inhibitory Activity ◽

Phytochemical Constituents ◽

Inhibitory Activities ◽

Ellman’S Method

Acetylcholine (ACh) is an important neurotransmitter in the human brain and nervous system. Acetylcholinesterase inhibitors (AChEIs) are commonly used to improve cognitive function and exist in many plants, including Millingtonia hortensis. M. hortensis, a Thai medicinal plant, has been used as a smoke delivered bronchodilator. The aims of this study were to identify phytochemical constituents and evaluate the cholinesterase inhibitory activity of M. hortensis leaves and flower extracts. The phytochemical identifications were performed by gas chromatography-mass spectrometry. The inhibitory activities of acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) were measured through kinetic enzyme analysis by Ellman’s method. The results showed that all the extracts exhibited specific AChEIs less than 30 % inhibition. While only the chloroform leaf extract inhibited BChE below 30 % inhibitory activities at 5.0 mg/mL. The GC-MS fingerprints revealed 15 main phytochemical constituents in the crude extracts. Additionally, all plant extracts showed antioxidant activity. The leaf extracts were non-poisonous when AChE activity is decreased by 20 - 30 % compared to normal AChE activity.

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Synthesis and Evaluation of 5-Benzyl-1,3,4-Thiadiazole Derivatives as Acetylcholinesterase Inhibitors

Journal of Chemical Research ◽

10.3184/174751917x15094552081242 ◽

2017 ◽

Vol 41 (11) ◽

pp. 664-667

Author(s):

Da-Hua Shi ◽

Hui-Long Zhu ◽

Yu-Wei Liu ◽

Zong-Ming Tang ◽

Chen Lu ◽

...

Keyword(s):

Diffraction Analysis ◽

Phenylacetic Acid ◽

Inhibitory Concentration ◽

Acetylcholinesterase Inhibitors ◽

Acetylcholinesterase Inhibition ◽

Inhibition Activity ◽

X Ray Diffraction ◽

Operating Environment ◽

X Ray ◽

Thiadiazole Derivatives

Three novel 5-benzyl-1,3,4-thiadiazole derivatives were synthesised starting from phenylacetic acid derivatives. These compounds were characterised by NMR, HRMS and single-crystal X-ray diffraction analysis. 2-Pyrrolidyl-5-[2-(4-bromophenyl)methyl]-1,3,4-thiadiazole showed moderate acetylcholinesterase-inhibition activity with a 50% inhibitory concentration value of 33.16 μM. 2-Pyrrolidyl-5-[2-(4-bromophenyl)methyl]-1,3,4-thiadiazole and acetylcholinesterase docking was demonstrated using the Molecular Operating Environment program.

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Acetyl-cholinesterase Inhibition by Extracts and Isolated Flavones from Linaria reflexa Desf. (Scrophulariaceae)

Natural Product Communications ◽

10.1177/1934578x0700200711 ◽

2007 ◽

Vol 2 (7) ◽

pp. 1934578X0700200 ◽

Cited By ~ 3

Author(s):

Monica Rosa Loizzo ◽

Rosa Tundis ◽

Federica Menichini ◽

Marco Bonesi ◽

Giancarlo Antonio Statti ◽

...

Keyword(s):

Dose Response ◽

Acetylcholinesterase Inhibition ◽

Activity Relationship ◽

Cholinesterase Inhibition ◽

Inhibition Activity ◽

Response Relationship ◽

Acetyl Cholinesterase ◽

Dose Response Relationship ◽

Structure Activity ◽

Ellman’S Method

Extracts, linariin, isolinariin A and B obtained from Linaria reflexa Desf. (Scrophulariaceae) were tested for acetylcholinesterase inhibition activity using Ellman's method. A dose-response relationship was observed for all extracts and isolated compounds. Flavones exhibited IC50 values ranging from 0.27 μM to 0.30 μM. The structure-activity relationship was briefly discussed.

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Synthesis, in vitro Acetylcholinesterase Inhibitory Activity Evaluation and Docking Investigation of Some Aromatic Chalcones

MedPharmRes ◽

10.32895/ump.mpr.1.1.15/suffix ◽

2017 ◽

Vol 1 (1) ◽

pp. 15-25

Author(s):

Dao Tran ◽

Son Tran ◽

Vi Nguyen ◽

Tri Le ◽

Minh Thai ◽

...

Keyword(s):

Inhibitory Activity ◽

Condensation Reaction ◽

Acetylcholinesterase Inhibitors ◽

Docking Studies ◽

Acetylcholinesterase Inhibitory Activity ◽

Ic50 Value ◽

Ic50 Values ◽

Inhibitory Activities ◽

Ellman’S Method

In this study, a total of twenty chalcones were synthesized via Claisen-Schmidt condensation reaction and evaluated for their in vitro acetylcholinesterase inhibitory activities using Ellman’s method. Molecular docking studies on acetylcholinesterase were performed to elucidate the interactions between these chalcone derivatives and acetylcholinesterase active site at the molecular level. From the series, six compounds (S1-5 and S17) exhibited strong acetylcholinesterase inhibitory activities with IC50 values below 100 µM compared to the parent unsubstituted chalcone. Compound S17 (4’-amino-2-chlorochalcone) showed the strongest acetylcholinesterase inhibitory activity in the investigated group with IC50 value of 36.10 µM. Molecular modeling studies were consistent with the results of in vitro acetylcholinesterase inhibitory activities, and chalcone S17 could be considered as a potential lead compound for the development of new acetylcholinesterase inhibitors.

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Synthesis, characterization, crystal structures, and the biological evaluation of 2-phenylthiazole derivatives as cholinesterase inhibitors

Journal of Chemical Research ◽

10.1177/1747519820976543 ◽

2020 ◽

pp. 174751982097654

Author(s):

Da-Hua Shi ◽

Meng-qiu Song ◽

Xiao-Dong Ma ◽

Jia-Bin Su ◽

Jing Wang ◽

...

Keyword(s):

Cholinesterase Inhibitors ◽

Docking Study ◽

Biological Evaluation ◽

Acetylcholinesterase Inhibition ◽

Cholinesterase Inhibition ◽

Resonance Spectroscopy ◽

Inhibition Activity ◽

X Ray Diffraction ◽

Anionic Site ◽

Ellman’S Method

Four 2-phenylthiazole derivatives are synthesized, characterized, and evaluated as cholinesterase inhibitors. The structures of the 2-phenylthiazole derivatives are confirmed by 1H and 13C nuclear magnetic resonance spectroscopy, single-crystal X-ray diffraction studies, and Hirshfeld surfaces analysis. Hirshfeld surface analysis of the prepared compounds showed C–H···O intermolecular interactions. The cholinesterase inhibition activities of the synthesized compounds are tested by Ellman’s method. [2-(4-Benzyloxyphenyl)-thiazol-4-yl]-(3,5-dimethylpiperidin-1-yl)-methanone showed the best acetylcholinesterase inhibition activity with an IC50 value of 8.86 µM and the best butyrylcholinesterase inhibition activity with an IC50 value of 1.03 µM. A docking study demonstrates that the same compound interacts with the catalytic anionic site and peripheral anionic site of acetylcholinesterase and the catalytic anionic site of butyrylcholinesterase.

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Synthesis and AChE inhibitory activity of N-glycosyl benzofuran derivatives

Heterocyclic Communications ◽

10.1515/hc-2019-0021 ◽

2019 ◽

Vol 25 (1) ◽

pp. 162-166

Author(s):

Yu-Ran Wu ◽

Shu-Ting Ren ◽

Lei Wang ◽

Xiu-Jian Liu ◽

You-Xian Wang ◽

...

Keyword(s):

Carboxylic Acids ◽

Inhibitory Activity ◽

Acetylcholinesterase Inhibition ◽

Inhibition Activity ◽

Reaction Conditions ◽

Inhibitory Rate ◽

Organic Bases ◽

Ache Inhibitory Activity ◽

Ellman’S Method

AbstractSix N-glycosyl benzofuran derivatives were synthesized by the catalysis of organic bases and condensation agents. The benzofuran derivatives were obtained by the reaction of various salicylaldehydes in acetone, and then hydrolyzed to the corresponding carboxylic acids. Finally, the target compounds were synthesized by acylation and the reaction conditions were optimized. The acetylcholinesterase (AChE) inhibitory activity of the desired compounds was tested using Ellman’s method. Most of the compounds showed acetylcholinesterase-inhibition activity; N-(2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)benzofuran-2-carbxamide (5a) showed the best acetylcholinesterase inhibition, with an inhibitory rate of 84%.

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