Novel 2-Arylbenzimidazole derivatives as multi-targeting agents to treat Alzheimer’s disease

Tan, Oya Ünsal; Özadali-Sari, Keriman; Ayazgök, Beyza; Küçükkılınç, Tuba Tüylü; Balkan, Ayla

doi:10.1007/s00044-017-1874-1

Cited by 11 publications

(6 citation statements)

References 40 publications

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“…This property facilitated a systematic investigation [ 19 , 20 , 21 ]. When the literature studies are evaluated, it can be learned that benzazole derivatives have inhibitory activity on acetylcholinesterase enzyme [ 17 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. In addition, some benzimidazole derivatives have been shown to be useful as amyloid imaging probes because of their high binding affinity to Aβ aggregates and high uptake into the brain [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives

et al. 2019

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Alzheimer’s disease (AD), one of the main causes of aged dementia, is a progressive and degenerative neurological disorder characterized by loss of cognition and memory. Although the symptomatic treatment of AD, particularly acetylcholinesterase inhibitors (AChEIs) based on the ‘cholinergic hypothesis’, has been successful in clinic, at present there is no cure for this disease. In this study, we designed compounds carrying benzimidazole and triazole rings on the same chemical skeleton so as to investigate their potential acetylcholinesterase and butyrylcholinesterase activity. Furthermore, molecular modeling study was performed to determine the binding mode of the best inhibitor to the AChE. Among them, compounds 3d and 3h, which featured 3,4-dihydroxy substitution at the phenyl ring and 5(6)-chloro substitution at the benzimidazole ring were found to be potent inhibitors of AChE. The inhibition kinetics of the two most active derivatives 3d and 3h were further studied. The kinetic displayed increasing slope and increasing intercept, which is consistent with a mixed inhibition. The IC50 and Ki values of 3d are 31.9 ± 0.1 nM and 26.2 nM, respectively. Compound 3h exhibited IC50 of 29.5 ± 1.2 nM and Ki of 24.8 nM. The above data compared favorably with data for donepezil (21.8 ± 0.9 nM) the reference compound in our study.

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Section: Introductionmentioning

confidence: 99%

Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives

et al. 2019

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“…In this study, a modified oligomeric Aβ (1–42) neurotoxicity analysis protocol was applied in order to elucidate the effects of treatment groups on SH-SY5Y cell viability in the presence of Aβ [ 56 ]. In order to model Aβ-induced neurotoxicity in vitro , an oligomeric form of the Aβ1–42 peptide was prepared by diluting with ice-cold Ham’s F12 Nutrient Mixture medium dissolved in PBS containing 0.02 M NaOH at a final concentration of 50 μM and kept in a 37°C incubator for 7 days to form peptide aggregates prior to the experiments [ 57 , 58 ]. 5x10 3 SH-SY5Y cells were differentiated inside the xCELLigence instrument for 5 days and treated with 100 nM TSA, RG108, givinostat, rifampin; 100 ng/ml LPS+IFN-ɣ or 1 μg/ml CFS+IFN-ɣ for 24 h in order to evaluate neuroprotection.…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective effects of some epigenetic modifying drugs’ on Chlamydia pneumoniae-induced neuroinflammation: A novel model

Tilki

Dikmen

2021

PLoS ONE

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Chlamydia pneumoniae (Cpn) is a gram-negative intracellular pathogen that causes a variety of pulmonary diseases, and there is growing evidence that it may play a role in Alzheimer’s disease (AD) pathogenesis. Cpn can interact functionally with host histones, altering the host’s epigenetic regulatory system by introducing bacterial products into the host tissue and inducing a persistent inflammatory response. Because Cpn is difficult to propagate, isolate, and detect, a modified LPS-like neuroinflammation model was established using lyophilized cell free supernatant (CFS) obtained from infected cell cultures, and the effects of CFS were compared to LPS. The neuroprotective effects of Trichostatin A (TSA), givinostat, and RG108, which are effective on epigenetic mechanisms, and the antibiotic rifampin, were studied in this newly introduced model and in the presence of amyloid beta (Aβ) 1–42. The neuroprotective effects of the drugs, as well as the effects of CFS and LPS, were evaluated in Aβ-induced neurotoxicity using a real-time cell analysis system, total ROS, and apoptotic impact. TSA, RG108, givinostat, and rifampin all demonstrated neuroprotective effects in both this novel model and Aβ-induced neurotoxicity. The findings are expected to provide early evidence on neuroprotective actions against Cpn-induced neuroinflammation and Aβ-induced neurotoxicity, which could represent a new treatment option for AD, for which there are currently few treatment options.

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“…It was determined that the methoxy group attached to the benzimidazole ring increased the cholinesterase inhibitory activity and inhibited aβ aggregation well (Figure 13). [45] …”

Section: Benzimidazoles and Benzoxazoles In Alzheimer's Disease Treat...mentioning

confidence: 99%

“…[42][43][44] 13). [45] Faraji et al synthesized a series of 20 new benzimidazole and benzothiazole derivatives bound to the 1,2,3-triazole ring system and investigated the AChE inhibitory activity of these compounds. A triazole group was formed by a series of reactions to the synthesized benzoimidazole ring of 2-mercaptobenzimidazole and its 5-methyl derivative.…”

Section: Benzimidazoles and Benzoxazoles In Alzheimer's Disease Treat...mentioning

confidence: 99%

Benzimidazole and Benzoxazole Derivatives Against Alzheimer's Disease

Faydalı,

Arpacı

2024

Chemistry & Biodiversity

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Benzimidazole and benzoxazole derivatives are included in the category of medical drugs in a wide range of areas such as anticancer, anticoagulant, antihypertensive, anti‐inflammatory, antimicrobial, antiparasitic, antiviral, antioxidant, immunomodulators, proton pump inhibitors, hormone modulators, etc. Many researchers have focused on synthesizing more effective benzimidazole and benzoxazole derivatives for screening various biological activities. In addition, there are benzimidazole and benzoxazole rings as bioisosteres of aromatic rings found in drugs used in the treatment of Alzheimer's disease. Because of the diverse activity of the benzimidazole and benzoxazole rings and bioisosteres marketed as drugs for Alzheimer Diseases, designed compounds containing these rings are likely to be effective against Alzheimer's disease. In this study, the effectiveness of compounds containing benzimidazole and benzoxazole rings against Alzheimer's disease will be examined.

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Novel 2-Arylbenzimidazole derivatives as multi-targeting agents to treat Alzheimer’s disease

Cited by 11 publications

References 40 publications

Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives

Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives

Neuroprotective effects of some epigenetic modifying drugs’ on Chlamydia pneumoniae-induced neuroinflammation: A novel model

Benzimidazole and Benzoxazole Derivatives Against Alzheimer's Disease

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