Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase inhibitors

Nisa, Mehrun; Munawar, Munawar Ali; Iqbal, Amber; Ahmed, Asrar; Ashraf, Muhammad; Gardener, Qurra-tul-Ann A.; Khan, Misbahul Ain

doi:10.1016/j.ejmech.2017.06.036

Cited by 20 publications

(16 citation statements)

References 22 publications

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“…However, chronic exposure to donepezil has been reported to induce severe dose‐dependent adverse effects on zebrafish behavior (Audira et al, 2020). In our study, the decrease in AChE activity by DLX is in agreement with previous studies in which antidepressants, such as citalopram, fluoxetine, paroxetine, sertraline, and several structural derivatives of escitalopram, reduce cholinesterase expression (Müller et al, 2002; Munawar et al, 2015; Nisa et al, 2017; Rockwood et al, 2011). In particular, DLX‐treated rats show a decline in cholinesterase and improved cognition (Shaik et al, 2019).…”

Section: Discussionsupporting

confidence: 93%

Duloxetine ameliorates valproicacid‐inducedhyperactivity, anxiety‐like behavior, and social interaction deficits in zebrafish

et al. 2021

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Syndromic autism spectrum disorders (ASDs) are characterized by impaired social communication and repetitive/stereotyped behaviors. Currently available therapeutic agents against ASD have limited efficacy. Thus, searching for novel and effective drugs ameliorating core symptoms, in particular social deficits, is of utmost importance. Duloxetine (DLX), an antidepressant that has been identified as an agonist mimetic for the cell adhesion molecule L1, exhibits beneficial functions in vitro and in vivo. Therefore, in this study, we focused on the rapid and persistent neuroprotective function of DLX following valproic acid (VPA)‐triggered hyperactivity, anxiety‐like behavior and social deficits in zebrafish. Embryonic exposure to VPA reduced survival in a dose‐ and time‐dependent manner, delayed hatching, and also resulted in a significant number of malformed larvae. After initial dose–response experiments in zebrafish larvae, 10 μM VPA exposure between 0.33 and 4.5 days post fertilization (dpf) was identified as an effective concentration that led to an early and persistent ASD‐like phenotype in zebrafish. ASD‐like elevated acetylcholine esterase (AChE) activity and reduced Akt–mTOR signaling was observed in zebrafish whole brain. Acute administration of DLX (4.5–6 dpf) reduced the VPA‐induced ASD‐like phenotype in zebrafish larvae. Additionally, such early‐life acute DLX treatment had long‐term effects in ameliorating social impairments, hyperactivity, and anxiety‐like behaviors through adulthood. This was accompanied by reduced AChE activity and by normalized Akt–mTOR signaling. Overall, DLX treatment showed a long‐term therapeutic effect on autistic‐like behaviors, and alteration of AChE activity and Akt–mTOR signaling were identified as crucial in the VPA‐induced ASD zebrafish model.

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Section: Discussionsupporting

confidence: 93%

Duloxetine ameliorates valproicacid‐inducedhyperactivity, anxiety‐like behavior, and social interaction deficits in zebrafish

et al. 2021

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“…In earlier studies, antidepressants such as citalopram, fluoxetine, paroxetine, sertraline, and several structural derivatives of escitalopram significantly inhibited cholinesterases. [34][35][36][37] Consistent with earlier studies, rivastigmine and escitalopram caused further decline in AChE enzyme levels, thereby protecting and sustaining the function of remaining ACh from cholinergic nerve endings and improving cognition which was evident from the results of MWM trials in the present study. Furthermore, duloxetine-treated rats showed a decline in cholinesterase and improved cognition.…”

Section: Discussionsupporting

confidence: 91%

Antidepressants Modulate Behavioral, Biochemical, and Histological Alterations Induced by Chronic Aluminum Chloride Administration in Wistar Rats

Shaik

Shenoy

Anupama

et al. 2019

Journal of Pharmacology and Pharmacotherapeutics

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“…Purity and homogeneity of known compounds were confirmed by measuring their m.p. for 1a [44], 1c [46], 1e [47], 1f [48], 1g [49], 1h-j [50], 2d [49], 2g [51], 4b [89], 4c [90], 6a [60], 6d [91], 6e [57], 6f [92], 7a [93], 7b [56], 7d [61], 7f [62], 8b [94], and 8c [95], or boiling points for 6b [96], 7e [97], FT-IR spectra for 1a [51], 1g [52], 1h-i [50], 2g [51], 1 H-and 13 C-NMR spectra for 1c [46], 1e [47], 1f [48], 1g [46], 1h-j [50], 2c [48], 2d [53] and/or HRMS for 2c [48], and comparing them with literature data. All new hydrazide-hydrazones 1b, 1d, 2a-b, 2e-f, 2h, 3a-g, were fully characterized.…”

Section: Reagents and Materialsmentioning

confidence: 99%

Synthesis and Structure-Activity Relationship Studies of Hydrazide-Hydrazones as Inhibitors of Laccase from Trametes versicolor

et al. 2020

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A series of hydrazide-hydrazones 1–3, the imine derivatives of hydrazides and aldehydes bearing benzene rings, were screened as inhibitors of laccase from Trametes versicolor. Laccase is a copper-containing enzyme which inhibition might prevent or reduce the activity of the plant pathogens that produce it in various biochemical processes. The kinetic and molecular modeling studies were performed and for selected compounds, the docking results were discussed. Seven 4-hydroxybenzhydrazide (4-HBAH) derivatives exhibited micromolar activity Ki = 24–674 µM with the predicted and desirable competitive type of inhibition. The structure–activity relationship (SAR) analysis revealed that a slim salicylic aldehyde framework had a pivotal role in stabilization of the molecules near the substrate docking site. Furthermore, the presence of phenyl and bulky tert-butyl substituents in position 3 in salicylic aldehyde fragment favored strong interaction with the substrate-binding pocket in laccase. Both 3- and 4-HBAH derivatives containing larger 3-tert-butyl-5-methyl- or 3,5-di-tert-butyl-2-hydroxy-benzylidene unit, did not bind to the active site of laccase and, interestingly, acted as non-competitive (Ki = 32.0 µM) or uncompetitive (Ki = 17.9 µM) inhibitors, respectively. From the easily available laccase inhibitors only sodium azide, harmful to environment and non-specific, was over 6 times more active than the above compounds.

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Synthesis of novel 5-(aroylhydrazinocarbonyl)escitalopram as cholinesterase inhibitors

Cited by 20 publications

References 22 publications

Duloxetine ameliorates valproicacid‐inducedhyperactivity, anxiety‐like behavior, and social interaction deficits in zebrafish

Duloxetine ameliorates valproicacid‐inducedhyperactivity, anxiety‐like behavior, and social interaction deficits in zebrafish

Antidepressants Modulate Behavioral, Biochemical, and Histological Alterations Induced by Chronic Aluminum Chloride Administration in Wistar Rats

Synthesis and Structure-Activity Relationship Studies of Hydrazide-Hydrazones as Inhibitors of Laccase from Trametes versicolor

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