Discovery of Novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole Derivatives as Potential Anti‐Inflammatory Agents

Li, Qing; Hu, Qinghua; Wang, Xinning; Zong, Yang; Zhao, Leilei; Xing, Junpeng; Zhou, Jinpei; Zhang, Huibin

doi:10.1111/cbdd.12513

Cited by 13 publications

(5 citation statements)

References 34 publications

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“…Fluorophenyl-imidazole was capable of inhibiting nitric oxide metabolites and proinflammatory cytokines. Other studies tested imidazole-containing compounds as a potential anti-inflammatory agent in vitro and found that it inhibits oxide nitric and several proinflammatory cytokines [31][32][33]. Imidazole compounds present structural affinity to bind and inhibit oxide nitric production due to structural similarity to the heme-ligand type that carries an imidazole or related heterocyclic donor group [34,35].…”

Section: Discussionmentioning

confidence: 99%

Interference in Macrophage Balance (M1/M2): The Mechanism of Action Responsible for the Anti-Inflammatory Effect of a Fluorophenyl-Substituted Imidazole

Salvan da Rosa,

Bramorski Mohr,

Lubschinski

et al. 2024

Mediators of Inflammation

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Traditionally, the treatment of inflammatory conditions has focused on the inhibition of inflammatory mediator production; however, many conditions are refractory to this classical approach. Recently, an alternative has been presented by researchers to solve this problem: The immunomodulation of cells closely related to inflammation. Hence, macrophages, a critical key in both innate and acquired immunity, have been presented as an alternative target for the development of new medicines. In this work, we tested the fluorophenyl-imidazole for its anti-inflammatory activity and possible immunomodulatory effect on RAW 264.7 macrophages. We also evaluated the anti-inflammatory effect of the compound, and the macrophage repolarization to M2 was confirmed by the ability of the compound to reduce the M1 markers TNF-α, IL-6, MCP-1, IL-12p70, IFN-γ, and TLR4, the high levels of p65 phosphorylated, iNOS and COX-2 mRNA expression, and the fact that the compound was not able to induce the production of M1 markers when used in macrophages without lipopolysaccharide (LPS) stimulation. Moreover, fluorophenyl-imidazole had the ability to increase the M2 markers IL-4, IL-13, CD206, apoptosis and phagocytosis levels, arginase-1, and FIZZ-1 mRNA expression before LPS stimulation. Similarly, it was also able to induce the production of these same M2 markers in macrophages without being induced with LPS. These results reinforce the affirmation that the fluorophenyl-imidazole has an important anti-inflammatory effect and demonstrates that this effect is due to immunomodulatory activity, having the ability to trigger a repolarization of macrophages from M1 to M2a. These facts suggest that this molecule could be used as an alternative scaffold for the development of a new medicine to treat inflammatory conditions, where the anti-inflammatory and proregenerative properties of M2a macrophages are desired.

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Section: Discussionmentioning

confidence: 99%

Interference in Macrophage Balance (M1/M2): The Mechanism of Action Responsible for the Anti-Inflammatory Effect of a Fluorophenyl-Substituted Imidazole

Salvan da Rosa,

Bramorski Mohr,

Lubschinski

et al. 2024

Mediators of Inflammation

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“…6 ). 24 In another report, compounds 72 and 73 prepared by Kumar et al exhibited significant analgesic and anti-inflammatory properties. 25 Among N -benzimidazol-1-yl methyl-benzamide derivatives synthesized by Sethi et al , compound 74 displayed significant analgesic and anti-inflammatory activity ( Fig.…”

Section: Introductionmentioning

confidence: 95%

Recent achievements in the synthesis of benzimidazole derivatives

Chung,

Dung,

Duc

2023

RSC Adv.

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“…Mariappan et al ( Mariappan et al, 2015 ) synthesized a set of 2-substituted benzimidazole derivatives and reported that compounds 126–128 were found to be the most promising agents among the series displaying significant ( p < 0.01) analgesic and anti-inflammatory effect at a dose level of 100 mg/kg p.o. Li et al ( Li et al, 2015 ) assessed the synthesized two series of 2-(piperidin-4-yl)-1 H -benzo[d]imidazole derivatives for anti-inflammatory activity and found that the compound 129 exhibited the most potent inhibitory activity on nitric oxide and TNF-α production (IC 50 = 0.86 and 1.87 µM, respectively). Interestingly, the compound 129 also prevented 33.30 and 50.60% ear oedema in xylene-treated mice at doses of 4 and 12 mg/kg, respectively, compared to standard ibuprofen (26.77 and 39.34% inhibition at 4 and 12 mg/kg dose levels, respectively).…”

Section: Biological Activitiesmentioning

confidence: 99%

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

et al. 2021

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Nowadays, nitrogenous heterocyclic molecules have attracted a great deal of interest among medicinal chemists. Among these potential heterocyclic drugs, benzimidazole scaffolds are considerably prevalent. Due to their isostructural pharmacophore of naturally occurring active biomolecules, benzimidazole derivatives have significant importance as chemotherapeutic agents in diverse clinical conditions. Researchers have synthesized plenty of benzimidazole derivatives in the last decades, amidst a large share of these compounds exerted excellent bioactivity against many ailments with outstanding bioavailability, safety, and stability profiles. In this comprehensive review, we have summarized the bioactivity of the benzimidazole derivatives reported in recent literature (2012–2021) with their available structure-activity relationship. Compounds bearing benzimidazole nucleus possess broad-spectrum pharmacological properties ranging from common antibacterial effects to the world’s most virulent diseases. Several promising therapeutic candidates are undergoing human trials, and some of these are going to be approved for clinical use. However, notable challenges, such as drug resistance, costly and tedious synthetic methods, little structural information of receptors, lack of advanced software, and so on, are still viable to be overcome for further research.

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Discovery of Novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole Derivatives as Potential Anti‐Inflammatory Agents

Cited by 13 publications

References 34 publications

Interference in Macrophage Balance (M1/M2): The Mechanism of Action Responsible for the Anti-Inflammatory Effect of a Fluorophenyl-Substituted Imidazole

Interference in Macrophage Balance (M1/M2): The Mechanism of Action Responsible for the Anti-Inflammatory Effect of a Fluorophenyl-Substituted Imidazole

Recent achievements in the synthesis of benzimidazole derivatives

A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives

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