Exploration of 2-benzylbenzimidazole scaffold as novel inhibitor of NF-κB

Boggu, Pulla Reddy; Venkateswararao, Eeda; Manickam, Manoj; Kwak, Dajin; Kim, Youngsoo; Jung, Sang‐Hun

doi:10.1016/j.bmc.2016.03.012

Cited by 27 publications

(17 citation statements)

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“…Many established reports demonstrated that the benzimidazole nucleus-containing drugs are highly suitable to produce beneficial effects against neuronal death in many neurodegenerative disease models [51][52][53]. Reportedly, benzimidazole derivatives act not only as an endogenous potent anti-oxidant and free radical scavenger in various pathological and disease conditions [54,55], but also as an activator of many antioxidant systems. In particular, they activate superoxide dismutase (SODs), GSH, Sirtuins (SIRTs), and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway.…”

Section: Discussionmentioning

confidence: 99%

Benzimidazole Containing Acetamide Derivatives Attenuate Neuroinflammation and Oxidative Stress in Ethanol-Induced Neurodegeneration

et al. 2020

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Oxidative stress-induced neuroinflammation is the prominent feature of neurodegenerative disorders, and is characterized by a gradual decline of structure and function of neurons. Many biochemical events emerge thanks to the result of this neurodegeneration, and ultimately provoke neuroinflammation, activation of microglia, and oxidative stress, leading to neuronal death. This cascade not only explains the complexity of events taking place across different stages, but also depicts the need for more effective therapeutic agents. The present study was designed to investigate the neuroprotective effects of newly synthesized benzimidazole containing acetamide derivatives, 3a (2-(4-methoxyanilino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) and 3b (2-(Dodecylamino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) against ethanol-induced neurodegeneration in the rat model. Both derivatives were characterized spectroscopically by proton NMR (1H-NMR) and carbon-13 NMR (13C-NMR) and evaluated for neuroprotective potential using different pharmacological approaches. In vivo experiments demonstrated that ethanol triggered neurodegeneration characterized by impaired antioxidant enzymes and elevated oxidative stress. Furthermore, ethanol administration induced neuroinflammation, as demonstrated by elevated expression of tumor necrotic factor (TNF-α), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX2), and ionized calcium-binding adapter molecule-1 (Iba-1), which was further validated by enzyme-linked immunosorbent assay (ELISA). Treatment with 3a and 3b ameliorated the ethanol-induced oxidative stress, neuroinflammation, and memory impairment. The affinity of synthesized derivatives towards various receptors involved in neurodegeneration was assessed through docking analysis. The versatile nature of benzimidazole nucleus and its affinity toward several receptors suggested that it could be a multistep targeting neuroprotectant. As repetitive clinical trials of neuroprotectants targeting a single step of the pathological process have failed previously, our results suggested that a neuroprotective strategy of acting at different stages may be more advantageous to intervene in the vicious cycles of neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

Benzimidazole Containing Acetamide Derivatives Attenuate Neuroinflammation and Oxidative Stress in Ethanol-Induced Neurodegeneration

et al. 2020

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“…All reagent-grade chemicals were obtained from commercial suppliers and were used as received. Unless otherwise indicated, 1 H and 13 C (NMR) spectra were recorded on a Bruker Advance III spectrometer at 1 H (300 MHz), 13 C (75 MHz)…”

Section: Materials Of Chemistrymentioning

confidence: 99%

Design, Synthesis and <i>in Vitro</i> Antibacterial Activity of 2-thiomethyl-benzimidazole Derivatives

Evrard¹,

Coulibali²,

Etienne³

et al. 2021

ABC

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A series of novel substituted benzimidazole (7a -n) derivatives were synthesized and characterized by 1 H, 13 C Nuclear Magnetic Resonance (NMR) spectra and High Resolution Mass Spectrometry (HRMS). The substitution was done in position -1 and -2 by appropriate groups. These compounds are obtained by N-alkylation reaction with thiomethyl-1H-benzimidazole intermediates (5a -g). Design of intermediates (5a -g) was made by condensation reaction between 2-methylbenzimidazole thiourunium salt (3) and functionalized halides (4) in the presence of sodium hydroxide (NaOH). Among the twenty-one compounds synthesized, ten were evaluated for their antimicrobial activity on three bacterial strains namely: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853. Only E. coli ATTC 25922 was susceptible to the synthesized derivatives 5g, 7f and 7h with a significant antibacterial activity (CMI is between 250 and 500 μg/mL).

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“…Первый компонент, натриевая соль глутамилтриптофана (глу-трп), обладает свойствами тимомиметика, способен стимулировать экспрессию эндосомальных TLR 3, 7, 9 и снижать выработку TNFα и IL-6A в культурах клеток F231 [2,4]. Другой компонент -2-бензилбензимидазол гидрохлорид (бендазол) ингибирует NF-κB, причем бензимидазольный каркас выполняет функцию фармакофора [9]. Показано также, что бендазол снижает утечку ионов K + и вероятно уменьшает внутриклеточное содержание ионов Са 2+ [1].…”

Section: цитовир-3 (медицинская гипотеза)unclassified

Some opportunities for immunotherapy in coronavirus infection

Смирнов

Тотолян

2020

Russian Journal of Infection and Immunity

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Here we review means of immunomodulatory therapy for coronavirus infection caused by SARS-CoV-2 (COVID-19). It has been appreciated that highly limited arsenal of relatively effective means and methods of prevention and treatment of the COVID-19 pandemic is available. The goal of our study was to analyze some therapeutic approaches based on available publications for COVID-19 treatment viewed from acting via innate immunity system. Convalescent plasma serotherapy represents one of the means with verified therapeutic efficacy that was accompanied with decreased viral load and relief of the disease symptoms. The drawback of serotherapy results from limited number of potential plasma donors and profound variety in amount of SARS-CoV-2-specific antibodies found in donor plasma. Another approach to COVID-19 therapy is based on using monoclonal antibodies engineered to target specific virus antigenic determinants, most often surface spike antigen. Antibodies blocking such antigen are able to prevent virus entrance into target cells and development of overt infection. On the other hand, there are monoclonal antibodies abrogating production or binding of excessive amounts of pro-inflammatory cytokines, such as IL-6, TNFα, etc., some of which (tocilizumab) have been already tested in COVID-19 therapy, whereas the remaining preparations are being currently investigated and tested. A certain breakthrough in COVID-19 therapy was provided by the well-known drugs chloroquine and dihydrochloroquine, which have proven to be effective as antiviral, anti-inflammatory and immunomodulatory means. Finally, a new multicomponent immunomodulatory preparation Cytovir-3 has been proposed already passed clinical trials and recommended for use in prevention and treatment of influenza and SARS and might have found its own niche in preventing COVID-19, as SARS-CoV-2 also belongs to the group of acute respiratory viruses. Thus, the arsenal of means for COVID-19 prevention and treatment contains the drugs for immunomodulatory therapy and prevention of immune-related disorders developing in response to invasion pathogenic viruses and lowering a risk of possible damage. Hence, correct and scientifically justified use of such remedies will increase overall effectiveness of fight against the coronavirus pandemic.

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Exploration of 2-benzylbenzimidazole scaffold as novel inhibitor of NF-κB

Cited by 27 publications

References 17 publications

Benzimidazole Containing Acetamide Derivatives Attenuate Neuroinflammation and Oxidative Stress in Ethanol-Induced Neurodegeneration

Benzimidazole Containing Acetamide Derivatives Attenuate Neuroinflammation and Oxidative Stress in Ethanol-Induced Neurodegeneration

Design, Synthesis and <i>in Vitro</i> Antibacterial Activity of 2-thiomethyl-benzimidazole Derivatives

Some opportunities for immunotherapy in coronavirus infection

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Exploration of 2-benzylbenzimidazole scaffold as novel inhibitor of NF-κB

Cited by 27 publications

References 17 publications

Benzimidazole Containing Acetamide Derivatives Attenuate Neuroinflammation and Oxidative Stress in Ethanol-Induced Neurodegeneration

Benzimidazole Containing Acetamide Derivatives Attenuate Neuroinflammation and Oxidative Stress in Ethanol-Induced Neurodegeneration

Design, Synthesis and &lt;i&gt;in Vitro&lt;/i&gt; Antibacterial Activity of 2-thiomethyl-benzimidazole Derivatives

Some opportunities for immunotherapy in coronavirus infection

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Design, Synthesis and <i>in Vitro</i> Antibacterial Activity of 2-thiomethyl-benzimidazole Derivatives