Molecular docking studies of coumarin hybrids as potential acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A/B and β-amyloid inhibitors for Alzheimer’s disease

Yusufzai, Samina Khan; Khan, Azeem; Sulaiman, Othman; Osman, Hasnah; Lamjin, Dalily Nabilah

doi:10.1186/s13065-018-0497-z

Cited by 56 publications

(29 citation statements)

References 106 publications

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“… 24 , 25 To date, several computational studies have successfully identified novel ChE inhibitors. 14 , 26 − 29 Therefore, utilization of computational methods to identify novel ChE lead compounds is a well-known approach to discover innovative treatments for AD.…”

Section: Introductionmentioning

confidence: 99%

Structure-Based Scaffold Repurposing toward the Discovery of Novel Cholinesterase Inhibitors

et al. 2020

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Cholinesterases (ChE) are well-known drug targets for the treatment of Alzheimer's disease (AD). In continuation of work to develop novel cholinesterase inhibitors, we utilized a structure-based scaffold repurposing approach and discovered six novel ChE inhibitors from our recently developed DNA gyrase inhibitor library. Among the identified hits, two compounds (denoted 3 and 18) were found to be the most potent inhibitor of acetylcholinesterase (AChE, IC 50 = 6.10 ± 1.01 μM) and butyrylcholinesterase (BuChE, IC 50 = 5.50 ± 0.007 μM), respectively. Compound 3 was responsible for the formation of H-bond and π−π stacking interactions within the active site of AChE. In contrast, compound 18 was well fitted in the choline-binding pocket and catalytic site of BuChE. Results obtained from in vitro cytotoxicity assays and in silico derived physicochemical and absorption, distribution, metabolism, and excretion (ADME) properties indicate that repurposed scaffold 3 and 18 could be potential drug candidates for further development as novel ChE inhibitors.

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Section: Introductionmentioning

confidence: 99%

Structure-Based Scaffold Repurposing toward the Discovery of Novel Cholinesterase Inhibitors

et al. 2020

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“…Neuroprotective effect of compound 11h against damage induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] was investigated in PC12 cells by MTT assay. [24] This compound showed 6.4 % protection at the concentration of 25 μM comparing with rutin with 13.4 % protection at the same concentration.…”

Section: Neuroprotective Effect Against Aβ-induced Damage Measured Inmentioning

confidence: 99%

“…The formation of hydrophobic interactions through πÀ anion and πÀ π stack interactions of chromenone moiety of compound 11e with Gly115 as well as Glu197 and His438 from different positions were also observed. [27] The aromatic linker between arylisoxazole and chromenone moieties was completely fixed through πÀ alkyl and πÀ π stack interactions with Ala328 and Tyr332 residues in the protein's active site.…”

Section: Binding Interactions Mode Of Compoundsmentioning

confidence: 99%

“…The neuroprotective effect of compound 11h in protecting neuronal PC12 cells against damage induced by Aβ [25][26][27][28][29][30][31][32][33][34][35] was examined according to our previous report. [24] Molecular Docking Study A docking study was performed using Auto Dock Tools (version 1.5.6) and the pdb structures of 1EVE (AChE) and 1P0I (BChE) were taken from the Brookhaven protein database (http://www.rcsb.org).…”

Section: Neuroprotection Effect Against Aβ-induced Damagementioning

confidence: 99%

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Design and Synthesis of Novel Arylisoxazole‐Chromenone Carboxamides: Investigation of Biological Activities Associated with Alzheimer's Disease

Saeedi

Rastegari

Hariri

et al. 2020

Chemistry & Biodiversity

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IranThis article is dedicated to the memory of our unique teacher in Chemistry and Medicinal Chemistry, Professor Abbas Shafiee (1937 -2016).A novel series of hybrid arylisoxazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase (ChE) inhibitory activity based on the modified Ellman's method. Among synthesized compounds, 5-(3-nitrophenyl)-N-{4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2-oxazole-3-carboxamide depicted the most acetylcholinesterase (AChE) inhibitory activity (IC 50 = 1.23 μM) and 5-(3-chlorophenyl)-N-{4-[(2oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2-oxazole-3-carboxamide was found to be the most potent butyrylcholinesterase (BChE) inhibitor (IC 50 = 9.71 μM). 5-(3-Nitrophenyl)-N-{4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2oxazole-3-carboxamide was further investigated for its BACE1 inhibitory activity as well as neuroprotectivity and metal chelating ability as important factors involved in onset and progress of Alzheimer's disease. It could inhibit BACE1 by 48.46 % at 50 μM. It also showed 6.4 % protection at 25 μM and satisfactory chelating ability toward Zn 2 + , Fe 2 + , and Cu 2 + ions. Docking studies of 5-(3-nitrophenyl)-N-{4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2-oxazole-3-carboxamide and 5-(3-chlorophenyl)-N-{4-[(2-oxo-2H-1-benzopyran-7-yl)oxy]phenyl}-1,2-oxazole-3carboxamide confirmed desired interactions with those amino acid residues of the AChE and BChE, respectively.

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“…Coumarins represent a class of compounds with a broad spectrum of biological activities: anticancer, anti-HIV, antimicrobial, antithrombotic, antiviral, antioxidant and antiinflammatory [2,3]. Coumarin ring can be considered as a privileged scaffold and an ideal framework for the design of compounds that can interact with different targets [4][5][6].…”

mentioning

confidence: 99%

In silico Docking Study of Some Coumarin Derivatives as Potential Inhibitors on Different Dengue Viral Proteins

Tătărîngă¹,

Sathyamurthy²,

Sandu³

et al. 2019

Rev. Chim.

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Molecular docking studies of coumarin hybrids as potential acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A/B and β-amyloid inhibitors for Alzheimer’s disease

Cited by 56 publications

References 106 publications

Structure-Based Scaffold Repurposing toward the Discovery of Novel Cholinesterase Inhibitors

Structure-Based Scaffold Repurposing toward the Discovery of Novel Cholinesterase Inhibitors

Design and Synthesis of Novel Arylisoxazole‐Chromenone Carboxamides: Investigation of Biological Activities Associated with Alzheimer's Disease

In silico Docking Study of Some Coumarin Derivatives as Potential Inhibitors on Different Dengue Viral Proteins

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