Microwave-Assisted Organic Synthesis, structure–activity relationship, kinetics and molecular docking studies of non-cytotoxic benzamide derivatives as selective butyrylcholinesterase inhibitors

Wajid, Sheeba; Khatoon, Asma; Khan, Maria Aqeel; Zafar, Humaira; Kanwal, Shama; Atta-ur-Rahman, _; Choudhary, Muhammad Iqbal; Basha, Fatima Z.

doi:10.1016/j.bmc.2019.07.015

Cited by 18 publications

(7 citation statements)

References 49 publications

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“…Based on the previously reported AChE inhibitors, Wajid et al 203 introduced various substituents to benzamide structure to increase its selectivity against BChE. Compound 40 (Figure 13) was synthesized and it displayed an inhibitory preference for eq BChE with IC 50 value of 0.8 µM.…”

Section: The Interactions Between Ad and Bchementioning

confidence: 99%

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

Xing

Xiong

et al. 2020

Medicinal Research Reviews

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Structural information of butyrylcholinesterase (BChE) and its variants associated with several diseases are discussed here. Pure human BChE has been proved safe and effective in treating organophosphorus (OPs) poisoning and has completed Phase 1 and 2 pharmacokinetic (PK) and safety studies. The introduction of specific mutations into native BChE to endow it a self‐reactivating property has gained much progress in producing effective OPs hydrolases. The hydrolysis ability of native BChE on cocaine has been confirmed but was blocked to clinical application due to poor PK properties. Several BChE mutants with elevated cocaine hydrolysis activity were published, some of which have shown safety and efficiency in treating cocaine addiction of human. The increased level of BChE in progressed Alzheimer's disease patients made it a promising target to elevate acetylcholine level and attenuate cognitive status. A variety of selective BChE inhibitors with high inhibitory activity published in recent years are reviewed here. BChE could influence the weight and insulin secretion and resistance of BChE knockout (KO) mice through hydrolyzing ghrelin. The BChE‐ghrelin pathway could also regulate aggressive behaviors of BChE‐KO mice.

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Section: The Interactions Between Ad and Bchementioning

confidence: 99%

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

Xing

Xiong

et al. 2020

Medicinal Research Reviews

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“…[33] Some methoxy-naphthyl linked N-(1-benzylpiperidine) benzamide derivatives were found to inhibit AChE with IC 50 values in the range between 0.201 � 0.006 -1.442 � 0.026 μM and BuChE in the range between 0.68 � 0.04 -12.65 � 0.384 μM. [34] S. Wajid, et al [35] reported that some benzamide derivatives inhibited BuChE selectively with the IC 50 values range between 0.8 � 0.6 and 165 � 2.0 μM. The found that while compound did not inhibit electric eel AChE, 4-Bromo-N-(2,6-dichlorophenyl) benzamide had the highest inhibitory potency on equine serum BuChE.…”

Section: Resultsmentioning

confidence: 99%

“…(Figure 5B). S. Wajid, A. Khatoon [35] investigated the interactions of benzamide compounds with hBuChE by using Maestro Schrdinger2018-1. They discovered that Asp70, Glu197, Asn228, His438, and Thr523 are responsible for the majority of H bonds, as well as π-π interactions with Phe329.…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of Novel Dual Cholinesterase Inhibitors: In Vitro Inhibition Studies Supported with Molecular Docking

Koca

Güller

et al. 2022

Chemistry & Biodiversity

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The major cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are important in the therapy of Alzheimer's disease (AD) based on the cholinergic hypothesis. As a result, in recent years, the investigation of dual cholinesterase inhibition methods has become important among scientists. In this study, novel N‐(4‐chlorobenzyl)‐3,4‐dimethoxy‐N‐(m‐substituted)benzamide derivatives were synthesized. Then, inhibitory properties of these derivatives were examined in human AChE and BuChE in vitro and possible interactions were determined by molecular docking studies. All benzamide derivatives were exhibited dual inhibitory character and high BBB permeability. The most effective inhibitor was found as N7 for both AChE and BuChE with IC50 values of 1.57 and 2.85 μM, respectively. Besides the most potent inhibitor was predicted as N7 in terms of binding energies with −12.18 kcal/mol and −9.92 kcal/mol, respectively. The reason for these results is that bromine (N7) is the bulkiest molecule among the other substituted groups. These derivatives could be exploited to develop new medications for the treatment of central nervous system‐related diseases as AD by acting as dual inhibitors of AChE and BChE.

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“…Benzothienopyridine moiety was trapped in the anionic site through π – π stacking and π –alkyl interactions with Trp82. [ 24 ]…”

Section: Resultsmentioning

confidence: 99%

Thieno[2,3‐b]pyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer's disease

Saeedi

Safavi

Allahabadi

et al. 2020

Archiv der Pharmazie

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In search of safer tacrine analogs, various thieno[2,3-b]pyridine amine derivatives were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs). Among the synthesized compounds, compounds 5e and 5d showed the highest activity towards acetylcholinesterase and butyrylcholinesterase, with IC 50 values of 1.55 and 0.23 µM, respectively. The most active ChE inhibitors (5e and 5d) were also candidates for further complementary assays, such as kinetic and molecular docking studies as well as studies on inhibitory activity towards amyloidbeta (βA) aggregation and β-secretase 1, neuroprotectivity, and cytotoxicity against HepG2 cells. Our results indicated efficient anti-Alzheimer's activity of the synthesized compounds.

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Microwave-Assisted Organic Synthesis, structure–activity relationship, kinetics and molecular docking studies of non-cytotoxic benzamide derivatives as selective butyrylcholinesterase inhibitors

Cited by 18 publications

References 49 publications

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

Design and Synthesis of Novel Dual Cholinesterase Inhibitors: In Vitro Inhibition Studies Supported with Molecular Docking

Thieno[2,3‐b]pyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer's disease

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