Design, Synthesis, Molecular Docking, and Cholinesterase Inhibitory Potential of Phthalimide‐Dithiocarbamate Hybrids as New Agents for Treatment of Alzheimer's Disease

Asadi, Mehdi; Ebrahimi, Mostafa; Mohammadi‐Khanaposhtani, Maryam; Azizian, Homa; Sepehri, Saghi; Nadri, Hamid; Biglar, Mahmood; Amanlou, Massoud; Larijani, Bagher; Mirzazadeh, Roghieh; Edraki, Najmeh; Mahdavi, Mohammad

doi:10.1002/cbdv.201900370

Cited by 22 publications

(14 citation statements)

References 27 publications

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“…In recent years, rule of 5 [39] (including H‐bond donors<5, H‐bond acceptors<10, the molecular weight (MW)<500, CLogP<5 and rotatable bonds<10) and polar surface area <70 Å 2[40] have been used to predict the absorption and BBB permeability of compounds. The H‐bond acceptors, H‐bond donors and rotatable bonds values were calculated by the admet SAR server [41] . The MW, ClogP and polar surface area were calculated by ChemDraw 12.0.…”

Section: Resultsmentioning

confidence: 99%

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Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Yang

Qiao

Hui

et al. 2020

Chemistry & Biodiversity

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Four xanthone derivatives were synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) with metal chelating ability and antioxidant ability against Alzheimer's disease (AD). Most of them exhibited potential acetylcholinesterase (AChE), butylcholinesterase (BuChE) inhibitory, antioxidant and metal chelating properties. Among them, 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one had the highest ability to inhibit AChE and displayed high selectivity towards AChE (IC 50 = 2.403 � 0.002 μM for AChE and IC 50 = 31.221 � 0.002 μM for BuChE), and it was also a good antioxidant (IC 50 = 2.662 � 0.003 μM). Enzyme kinetic studies showed that this compound was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Interestingly, its copper complex showed more significant inhibitory activity for AChE (IC 50 = 0.934 � 0.002 μM) and antioxidant activity (IC 50 = 1.064 � 0.003 μM). Molecular dockings were carried out for the four xanthone derivatives in order to further investigate the binding modes. Finally, the blood-brain barrier (BBB) penetration prediction indicated that all compounds might penetrate BBB. These results suggested that 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one was promising AChEI with metal chelating ability and antioxidant ability for the further investigation.

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Section: Resultsmentioning

confidence: 99%

“…The H-bond acceptors, H-bond donors and rotatable bonds values were calculated by the admet SAR server. [41] The MW, ClogP and polar surface area were calculated by ChemDraw 12.0. The prediction of BBB penetration was also evaluated by the admet SAR server.…”

Section: Prediction Of Absorption and Bbb Permeabilitymentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Yang

Qiao

Hui

et al. 2020

Chemistry & Biodiversity

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“…8). 30 8). 31 Substituting the indanone fragment of donepezil with the benzamide or 2-picolinamide moiety introduced a novel MTDL that exhibited potent inhibitory activities towards MAO-A, MAO-B, and AChE.…”

Section: Replacement Of Indanone With Ferulic Acid Derivativesmentioning

confidence: 99%

The recent development of donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's agents: highlights from 2010 to 2020

et al. 2021

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“…Dithiocarbamate coupled with phthalimide is a competitive inhibitor of butyrylcholinesterase and acetylcholinesterase. This inhibitive property makes it suitable for the treatment of Alzheimer's Disease [106].…”

Section: Application Of Dithiocarbamate Compounds As Enzyme Inhibitormentioning

confidence: 99%

The Versatility in the Applications of Dithiocarbamates

Ajiboye

Marzouki

Onwudiwe

2022

IJMS

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Dithiocarbamate ligands have the ability to form stable complexes with transition metals, and this chelating ability has been utilized in numerous applications. The complexes have also been used to synthesize other useful compounds. Here, the up-to-date applications of dithiocarbamate ligands and complexes are extensively discussed. Some of these are their use as enzyme inhibitor and treatment of HIV and other diseases. The application as anticancer, antimicrobial, medical imaging and anti-inflammatory agents is examined. Moreover, the application in the industry as vulcanization accelerator, froth flotation collector, antifouling, coatings, lubricant additives and sensors is discussed. The various ways in which they have been employed in synthesis of other compounds are highlighted. Finally, the agricultural uses and remediation of heavy metals via dithiocarbamate compounds are comprehensively discussed.

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Design, Synthesis, Molecular Docking, and Cholinesterase Inhibitory Potential of Phthalimide‐Dithiocarbamate Hybrids as New Agents for Treatment of Alzheimer's Disease

Cited by 22 publications

References 27 publications

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

The recent development of donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's agents: highlights from 2010 to 2020

The Versatility in the Applications of Dithiocarbamates

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