Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors

Najafi, Zahra; Mahdavi, Mohammad; Saeedi, Mina; Karimpour-Razkenari, Elahe; Asatouri, Raymond; Vafadarnejad, Fahimeh; Moghadam, Farshad Homayouni; Khanavi, Mahnaz; Sharifzadeh, Mohammad; Akbarzadeh, Tahmineh

doi:10.1016/j.ejmech.2016.11.008

Cited by 96 publications

(45 citation statements)

References 34 publications

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“…The inhibitory potency of the target compounds on AChE and BChE was evaluated using Ellman's method . All compounds were dissolved in 1 mL DMSO and 9 mL ethanol and then four different concentrations (56.3, 11.3, 2.2, 0.45 μM per well) of each compound were tested to obtain the range of 20–80% enzyme inhibition for AChE/BChE.…”

Section: Methodsmentioning

confidence: 99%

“…Neuroprotective activity was evaluated as described in the literature . PC12 cell line was purchased from Pasteur institute.…”

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: 98%

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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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Section: Methodsmentioning

confidence: 99%

“…Neuroprotective activity was evaluated as described in the literature . PC12 cell line was purchased from Pasteur institute.…”

Section: Methodsmentioning

confidence: 99%

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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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“…[18] The rate of enzymatic reaction was obtained with different concentrations of inhibitor and in the absence of inhibitor. For this purpose, all experiments were per-formed similar to enzyme inhibition assay.…”

Section: Kinetic Studies Of Ache and Bche Inhibitionmentioning

confidence: 99%

Design and Synthesis of Selective Acetylcholinesterase Inhibitors: Arylisoxazole‐Phenylpiperazine Derivatives

Saeedi

Mohtadi-Haghighi

Mirfazli

et al. 2019

Chemistry & Biodiversity

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In this work, a novel series of arylisoxazole-phenylpiperazines were designed, synthesized, and evaluated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Our results revealed that [5-(2chlorophenyl)-1,2-oxazol-3-yl](4-phenylpiperazin-1-yl)methanone (5c) was the most potent AChE inhibitor with IC 50 of 21.85 μM. It should be noted that most of synthesized compounds showed no BChE inhibitory activity and [5-(2-fluorophenyl)-1,2-oxazol-3-yl](4-phenylpiperazin-1-yl)methanone (5a) was the most active anti-BChE derivative (IC 50 = 51.66 μM). Also, kinetic studies for the AChE and BChE inhibitory activity of compounds 5c and 5a confirmed that they have simultaneously bound to the catalytic site (CS) and peripheral anionic site (PAS) of both AChE and BChE. Furthermore, docking study of compound 5c showed desired interactions of that compound with amino acid residues located in the active and peripheral anionic sites. Compound 5c was also evaluated for its BACE1 inhibitory activity and demonstrated IC 50 = 76.78 μM. Finally, neuroprotectivity of compound 5c on Aβ-treated neurotoxicity in PC12 cells depicted low activity.

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“…Metal ions can bind to Aβ peptides and induce their aggregation. [3] Due to the complexity of AD, it is proposed to investigate multitargetdirected ligands (MTDLs). It is referred to activity of cholinesterase (ChE), especially two enzymes-acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE).…”

Section: Introductionmentioning

confidence: 99%

Novel tetrahydroacridine derivatives with iodobenzoic acid moiety as multifunctional acetylcholinesterase inhibitors

et al. 2017

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New synthesized series of 9-amino-1,2,3,4-tetrahydroacridine derivatives with iodobenzoic acid moiety were studied for their inhibitory activity toward cholinesterase and against β-amyloid aggregation. All novel molecules 3a-3i interacted with both cholinesterases-acetylcholinesterase and butyrylcholinesterase-delivered nanomolar IC values. The structure-activity relationship showed that N-butyl moiety derivatives are stronger inhibitors toward AChE and BuChE than N-ethyl and N-propyl moieties compounds. The most potent compound toward acetylcholinesterase was inhibitor 3f (IC = 31.2 nm), and it was more active than reference drug, tacrine (IC = 100.2 nm). Compound 3f showed strong inhibition of butyrylcholinesterase (IC = 8.0 nm), also higher than tacrine (IC = 16.3 nm). In the kinetic studies, compound 3f revealed mixed type of acetylcholinesterase inhibition. The computer modeling was carried out. The most active compound 3f was confirmed as peripheral anionic site inhibitor of acetylcholinesterase. Moreover, molecule 3f inhibited β-amyloid aggregation (at the concentration 10 μm-24.96% of inhibition, 25 μm-72%, 50 μm-78.44%, and 100 μm-84.92%). Therefore, among all examined, compound 3f is the most promising molecule for further, more detailed research of novel multifunctional agents in the therapy of Alzheimer's disease.

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Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors

Cited by 96 publications

References 34 publications

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

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

Design and Synthesis of Selective Acetylcholinesterase Inhibitors: Arylisoxazole‐Phenylpiperazine Derivatives

Novel tetrahydroacridine derivatives with iodobenzoic acid moiety as multifunctional acetylcholinesterase inhibitors

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