Synthesis, characterization, crystal structure and evaluation of four carbazole-coumarin hybrids as multifunctional agents for the treatment of Alzheimer’s disease

Shi, Da-Hua; Wei, Min; Song, Mijung; Li, Mingcheng; Zhang, Zhao-yuan; Liu, Yuwei; Liu, Weiwei

doi:10.1016/j.molstruc.2020.127897

Cited by 25 publications

(12 citation statements)

References 34 publications

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“…All the compounds showed greater inhibition of AChE than BuChE. In the designed compounds, the following structure-activity relationship were obtained: (i) compounds with a methyl group (3 b-f) on the coumarin scaffold (R 1 = CH 3 ) decreased the inhibitory activities of AChE more than the series of the compounds without the methyl group (3 h-l) except for 3 c, 3 i (n = 4), and 7 a and 7 g (linker as piperazine group), which was similar to other series of coumarin derivatives; [39,42] (ii) it was observed that the inhibitory activity toward AChE exhibited a notable rise in the compounds possessing longer hydrocarbon linkers, specifically in the cases of n = 4 to n = 12 for both series of IC 50 = 12.20 μM). It was possible that the active site of AChE consisted of many hydrophobic amino acids, such as phenylalanine and tryptophan, affecting the results for the of compounds 7 a, and 7 g, for which the linker piperazine displayed poor AChE inhibition.…”

Section: Cholinesterase Inhibitory Assay In 96-microtiter Well Platessupporting

confidence: 61%

Synthesis and Acetylcholinesterase Inhibitory Evaluation of Coumarin‐Linked Carbazole Derivatives

Tharamak,

Wisarutwanit,

Songoen

et al. 2023

ChemistrySelect

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The cholinesterase inhibitory activity was examined of synthetic carbazole‐coumarin hybrids, with long chain hydrocarbons, triazole, or piperazine as linkers. The most effective acetylcholinesterase inhibitor was 7‐((12‐(9H‐carbazol‐9‐yl)dodecyl)oxy)‐2H‐chromen‐2‐one (3 l), with an IC50 value of 6.86 μM and a high selectivity over butyrylcholinesterase. Compound 3 l also exhibited mixed‐type AChE inhibition in a kinetic study, with a Ki value of 4.87 μM. In addition, molecular docking of compound 3 l toward AChE was done to elucidate the inhibition at both the peripheral anionic and catalytic active sites. Furthermore, the HepG2 and Vero cells were unaffected by toxicity from compound 3 l. Therefore, these findings could be exploited to create a number of carbazole‐coumarin hybrids for future potential treatments for Alzheimer's disease.

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Section: Cholinesterase Inhibitory Assay In 96-microtiter Well Platessupporting

confidence: 61%

Synthesis and Acetylcholinesterase Inhibitory Evaluation of Coumarin‐Linked Carbazole Derivatives

Tharamak,

Wisarutwanit,

Songoen

et al. 2023

ChemistrySelect

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“…There are numerous accounts of the multifunctional carbazole moiety being utilized to treat AD. For instance, Choubdar, N. et al, developed new classes of carbazoles [ 88 ], Shi, D.H. et al, synthesized carbazole-coumarin hybrids [ 89 ], Bachurin, S.O. et al, synthesized novel conjugates of aminoadamantanes with carbazole derivatives [ 90 ], and Zhang, X. et al, developed novel multifunctional carbazole-amines [ 91 ].…”

Section: Inhibitionmentioning

confidence: 99%

A Review on Recent Approaches on Molecular Docking Studies of Novel Compounds Targeting Acetylcholinesterase in Alzheimer Disease

Peitzika

Pontiki

2023

Molecules

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Alzheimer’s disease (AD), a neurodegenerative brain disorder that affects millions of people worldwide, is characterized by memory loss and cognitive decline. Low levels of acetylcholine and abnormal levels of beta-amyloid, T protein aggregation, inflammation, and oxidative stress, have been associated with AD, and therefore, research has been oriented towards the cholinergic system and primarily on acetylcholinesterase (AChE) inhibitors. In this review, we are focusing on the discovery of AChE inhibitors using computer-based modeling and simulation techniques, covering the recent literature from 2018–2022. More specifically, the review discusses the structures of novel, potent acetylcholinesterase inhibitors and their binding mode to AChE, as well as the physicochemical requirements for the design of potential AChE inhibitors.

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“…In addition, 136 was able to bind both the CAS and PAS of cholinesterase, which suggested that it could interfere with PAS-induced β-amyloid aggregation. A different approach was followed by Shi and collaborators, who designed four derivatives obtained by coupling two pharmacophores (carbazole and coumarin) to obtain potential multitarget agents for the treatment of AD [170]. The aim was to exploit the biological activities of both the mentioned moieties: on one hand coumarins are known to have inhibitory activity on AChE, BuChE and MAO, besides antioxidant properties; on the other hand, carbazole exhibits antioxidant activity [171] and the ability to inhibit Aβ aggregation [172].…”

Section: Neuroprotection: Effect On Alzheimer's Diseasementioning

confidence: 99%

An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

Annunziata

Pinna

Dallavalle

et al. 2020

IJMS

251

156

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Privileged structures have been widely used as an effective template for the research and discovery of high value chemicals. Coumarin is a simple scaffold widespread in Nature and it can be found in a considerable number of plants as well as in some fungi and bacteria. In the last years, these natural compounds have been gaining an increasing attention from the scientific community for their wide range of biological activities, mainly due to their ability to interact with diverse enzymes and receptors in living organisms. In addition, coumarin nucleus has proved to be easily synthetized and decorated, giving the possibility of designing new coumarin-based compounds and investigating their potential in the treatment of various diseases. The versatility of coumarin scaffold finds applications not only in medicinal chemistry but also in the agrochemical field as well as in the cosmetic and fragrances industry. This review is intended to be a critical overview on coumarins, comprehensive of natural sources, metabolites, biological evaluations and synthetic approaches.

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Synthesis, characterization, crystal structure and evaluation of four carbazole-coumarin hybrids as multifunctional agents for the treatment of Alzheimer’s disease

Cited by 25 publications

References 34 publications

Synthesis and Acetylcholinesterase Inhibitory Evaluation of Coumarin‐Linked Carbazole Derivatives

Synthesis and Acetylcholinesterase Inhibitory Evaluation of Coumarin‐Linked Carbazole Derivatives

A Review on Recent Approaches on Molecular Docking Studies of Novel Compounds Targeting Acetylcholinesterase in Alzheimer Disease

An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

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