New classes of carbazoles as potential multi-functional anti-Alzheimer’s agents

Choubdar, Niloufar; Golshani, Mostafa; Jalili‐Baleh, Leili; Nadri, Hamid; Küçükkılınç, Tuba Tüylü; Ayazgök, Beyza; Moradi, Alireza; Moghadam, Farshad Homayouni; Abdolahi, Zahra; Ameri, Alieh; Salehian, Fatemeh; Foroumadi, Alireza; Khoobi, Mehdi

doi:10.1016/j.bioorg.2019.103164

Cited by 15 publications

(6 citation statements)

References 41 publications

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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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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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“…It has been reported that some carbazole derivatives are potential AD-modifying compounds, i.e., N -alkyl carbazoles are able to favor the formation of soluble form of Aβ, through different mechanisms [ 43 ] and are also able to block apoptosis, thus exerting a neuroprotective effect [ 44 ]. Moreover, recent studies suggested that some carbazole-based compounds are valuable anti-AD drug candidates, since they are able to inhibit both AChE and BChE activity [ 45 ] as well as AChE- and self-induced Aβ aggregation [ 46 ]. These findings support the rationale to develop novel hybrids with a multimodal profile by adding to biological properties of the carbazole core the neuroprotection derived by the memantine nucleus.…”

Section: Memantine and Cholinesterase Inhibitor Hybridsmentioning

confidence: 99%

Memantine Derivatives as Multitarget Agents in Alzheimer’s Disease

et al. 2020

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Memantine (3,5-dimethyladamantan-1-amine) is an orally active, noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist approved for treatment of moderate-to-severe Alzheimer’s disease (AD), a neurodegenerative condition characterized by a progressive cognitive decline. Unfortunately, memantine as well as the other class of drugs licensed for AD treatment acting as acetylcholinesterase inhibitors (AChEIs), provide only symptomatic relief. Thus, the urgent need in AD drug development is for disease-modifying therapies that may require approaching targets from more than one path at once or multiple targets simultaneously. Indeed, increasing evidence suggests that the modulation of a single neurotransmitter system represents a reductive approach to face the complexity of AD. Memantine is viewed as a privileged NMDAR-directed structure, and therefore, represents the driving motif in the design of a variety of multi-target directed ligands (MTDLs). In this review, we present selected examples of small molecules recently designed as MTDLs to contrast AD, by combining in a single entity the amantadine core of memantine with the pharmacophoric features of known neuroprotectants, such as antioxidant agents, AChEIs and Aβ-aggregation inhibitors.

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“…The results showed that carbazole derivatives are promising inhibitors for cholinesterase due to the interaction of the catalytic site and peripheral anionic site of AChE. [ 40 ] The obtained results showed that the substituted groups and metal atoms on the central cavity effects inhibition properties on enzymes.…”

Section: Resultsmentioning

confidence: 99%

Peripheral or nonperipheral tetra‐[4‐(9H‐carbazol‐9‐yl)phenoxy] substituted cobalt(II), manganese(III) phthalocyanines: Synthesis, acetylcholinesterase, butyrylcholinesterase, and α‐glucosidase inhibitory effects and anticancer activities

Barut

Keleş

Bıyıklıoğlu

et al. 2020

Applied Organom Chemis

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In this work, peripheral or nonperipheral tetra-[4-(9H-carbazol-9-yl)phenoxy] substituted cobalt(II), manganese (III) phthalocyanines were synthesized for the first time. Their acetylcholinesterase from Electrophorus electricus (AChE), butyrylcholinesterase equine serum (BuChE), and α-glucosidase Saccharomyces cerevisiae inhibition were investigated spectrophotometrically. Finally, in vitro cytotoxicities of the compounds were investigated on human neuroblastoma (SH-SY5Y) cell line using MTT cell viability assay. The compounds inhibited to enzymes in the range of 7.39 ± 0.25-35.29 ± 2.49 μM with IC 50 values for AChE and 14.38 ± 0.66-58.02 ± 4.94 μM for BuChE as compared with galantamine, which used as a positive control. For α-glucosidase, all compounds had stronger inhibition action than acarbose according to the IC 50 values. The IC 50 values of N Co and N Mn were found to be 3.05 ± 0.10 and 15.82 ± 1.85 μM, respectively. The results of cytotoxicity showed that the IC 50 values were above 100 μM showing the compounds had low cytotoxic action against SH-SY5Y cell line for 24 h. Overall, carbazole substituted nonperipheral compounds can be considered as a potential agent for the treatment of Alzheimer's diseases and diabetes mellitus.

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New classes of carbazoles as potential multi-functional anti-Alzheimer’s agents

Cited by 15 publications

References 41 publications

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

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

Memantine Derivatives as Multitarget Agents in Alzheimer’s Disease

Peripheral or nonperipheral tetra‐[4‐(9H‐carbazol‐9‐yl)phenoxy] substituted cobalt(II), manganese(III) phthalocyanines: Synthesis, acetylcholinesterase, butyrylcholinesterase, and α‐glucosidase inhibitory effects and anticancer activities

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