Design, Synthesis, Molecular Modeling and Anticholinesterase Activity of Benzylidene-Benzofuran-3-Ones Containing Cyclic Amine Side Chain

Mehrabi, Farzad; Pourshojaei, Yaghoub; Moradi, Alireza; Sharifzadeh, Mohammad; Khosravani, Leila; Sabourian, Reyhaneh; Rahmani-Nezhad, Samira; Mohammadi-Khanaposhtani, Maryam; Mahdavi, Mohammad; Asadipour, Ali; Rahimi, Hamid Reza; Moghimi, Setareh; Foroumadi, Alireza

doi:10.4155/fmc-2016-0237

Cited by 41 publications

(23 citation statements)

References 45 publications

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“…In 2017, Mehrabi et al. synthesized a series of benzylidene–benzofuran‐3‐ones as aurone analogues bearing cyclic amine side chains and studied their anticholinesterase activity . Compound 27 (Figure ) containing a piperidinylethoxy residue gives the best inhibitory activity against AChE, with an IC 50 value of 0.045 μ m .…”

Section: Discussionmentioning

confidence: 99%

Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

2018

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Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The Food and Drug Administration has approved drugs (e.g., rivastigmine, donepezil, galantamine, and memantine) that at best provide marginal benefits, thus emphasizing the urgent need to explore other molecular entities as future drug candidates for AD. Looking at the wide pharmaceutical applications of heterocyclic compounds and particularly those containing benzofuran and indole ring systems, these molecular frameworks have drawn special attention from medicinal chemists for further evaluation in numerous diseases. This article focuses on the history and recent advances of benzofuran- and indole-based compounds as inhibitors of butyrylcholinesterase, acetylcholinesterase, γ-secretase, β-secretase, tau misfolding, and β-amyloid aggregation.

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Section: Discussionmentioning

confidence: 99%

Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

2018

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“…Docking simulations for compound 7d was carried out by AutoDock Vina (AV) 1.1.1 program . The crystal structure of BChE (pdb code: 4BDS) was retrieved from Protein Data Bank.…”

Section: Methodsmentioning

confidence: 99%

“…In this context and as a continuation of our previous works on the synthesis of novel anti‐AD compounds, here we designed a new series of cinnamic acid–tryptamine hybrids 7a–l and evaluated their activity against AChE and BChE . Kinetic and docking studies of the synthesized compounds were also performed.…”

Section: Introductionmentioning

confidence: 99%

Novel cinnamic acid–tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study

Ghafary

Najafi

Mohammadi-Khanaposhtani

et al. 2018

Archiv der Pharmazie

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A novel series of cinnamic acid–tryptamine hybrids was designed, synthesized, and evaluated as cholinesterase inhibitors. Anticholinesterase assays showed that all of the synthesized compounds displayed a clearly selective inhibition of butyrylcholinesterase (BChE), but only a moderate inhibitory effect toward acetylcholinesterase (AChE) was detected. Among these cinnamic acid–tryptamine hybrids, compound 7d was found to be the most potent inhibitor of BChE with an IC50 value of 0.55 ± 0.04 μM. This compound showed a 14‐fold higher inhibitory potency than the standard drug donepezil (IC50 = 7.79 ± 0.81 μM) and inhibited BChE through a mixed‐type inhibition mode. Moreover, a docking study revealed that compound 7d binds to both the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of BChE. Also, compound 7d was evaluated against β‐secretase, which exhibited low activity (inhibition percentage: 38%).

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“…Docking study was performed by Autodock Tools (1.5.6) to predict the interaction mode of the most potent compounds 5g and 5d in the active site of AChE and BuChE, respectively. [29,30] Several ligandbounded crystallographic structures with various resolutions of AChE and BuChE are available in the RCSB protein data bank (http://www.rcsb.org/pdb/home/ home.do). Herein, PDB structure of 1EVE for AChE and 1P0I for BuChE were retrieved for docking purpose.…”

Section: Docking Studymentioning

confidence: 99%

Design, Synthesis, and Cholinesterase Inhibition Assay of Coumarin‐3‐carboxamide‐N‐morpholine Hybrids as New Anti‐Alzheimer Agents

Tehrani

Rezaei

Asadi

et al. 2019

Chemistry & Biodiversity

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A new series of coumarin‐3‐carboxamide‐N‐morpholine hybrids 5a–5l was designed and synthesized as cholinesterases inhibitors. The synthetic approach for title compounds was started from the reaction between 2‐hydroxybenzaldehyde derivatives and Meldrum's acid to afford corresponding coumarin‐3‐carboxylic acids. Then, amidation of the latter compounds with 2‐morpholinoethylamine or N‐(3‐aminopropyl)morpholine led to the formation of the compounds 5a–5l. The in vitro inhibition screen against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) revealed that most of the synthesized compounds had potent AChE inhibitory while their BuChE inhibitions are moderate to weak. Among them, propylmorpholine derivative 5g (N‐[3‐(morpholin‐4‐yl)propyl]‐2‐oxo‐2H‐chromene‐3‐carboxamide) bearing an unsubstituted coumarin moiety and ethylmorpholine derivative 5d (6‐bromo‐N‐[2‐(morpholin‐4‐yl)ethyl]‐2‐oxo‐2H‐chromene‐3‐carboxamide) bearing a 6‐bromocoumarin moiety showed the most activity against AChE and BuChE, respectively. The inhibitory activity of compound 5g against AChE was 1.78 times more than that of rivastigmine and anti‐BuChE activity of compound 5d is approximately same as rivastigmine. Kinetic and docking studies confirmed the dual binding site ability of compound 5g to inhibit AChE.

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Design, Synthesis, Molecular Modeling and Anticholinesterase Activity of Benzylidene-Benzofuran-3-Ones Containing Cyclic Amine Side Chain

Abstract: The anticholinesterase activities of benzylidene-benzofurane-3-ones as aurone analogs revealed that the compounds bearing piperidinylethoxy residue showed better activities against AChE, introducing these compounds for further drug discovery developments. [Formula: see text].

Cited by 41 publications

References 45 publications

Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

Novel cinnamic acid–tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study

Design, Synthesis, and Cholinesterase Inhibition Assay of Coumarin‐3‐carboxamide‐N‐morpholine Hybrids as New Anti‐Alzheimer Agents

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