Evaluation of the combined activity of benzimidazole arylhydrazones as new anti-Parkinsonian agents: monoamine oxidase-B inhibition, neuroprotection and oxidative stress modulation

Anastassova, Neda; Aluani, Denitsa; Kostadinov, Anton; Rangelov, Miroslav; Todorova, Nadezhda; Hristova-Avakumova, Nadya; Argirova, Maria; Lumov, Nikolay; Kondeva-Burdina, Magdalena; Tzankova, Virginia; Yancheva, Denitsa

doi:10.4103/1673-5374.309843

Cited by 18 publications

(13 citation statements)

References 44 publications

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“…4 Furthermore, many benzimidazoles are screened for their potential anti-inflammatory, 5 antiviral 6 antiproliferative, and anthelmintic properties. 7 Likely, these compounds exhibited potent free radical scavenging properties as demonstrated in several reports, 8,9 which can be attributed to neuroprotection in Parkinson's, 10 Alzheimer's, 11 and other memory impairment models. 12,13 In this context, the beneficial effects of benzimidazole against multiple neurodegenerative's targets have been recently reviewed.…”

Section: Introductionmentioning

confidence: 69%

Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment

Ullah¹,

Kury²,

Althobaiti³

et al. 2022

JIR

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The study investigated the effect of newly synthesized benzimidazole derivatives against ethanol-induced neurodegeneration. According to evidence, ethanol consumption may cause a severe insult to the central nervous system (CNS), resulting in mental retardation, neuronal degeneration, and oxidative stress. Targeting neuroinflammation and oxidative stress may be a useful strategy for preventing ethanol-induced neurodegeneration. Methodology: Firstly, the newly synthesized compounds were subjected to molecular simulation and docking in order to predict ligand binding status. Later, for in vivo observations, adult male Sprague Dawley rats were used for studying behavioral and oxidative stress markers. ELIZA kits were used to analyse tumour necrosis factor-alpha (TNF-), nuclear factor-B (NF-B), interleukin (IL-18), and pyrin domain-containing protein 3 (NLRP3) expression, while Western blotting was used to measure IL-1 and Caspase-1 expression. Results: Our findings suggested that altered levels of antioxidant enzymes were associated with elevated levels of TNF-α, NF-B, IL-1, IL-18, Caspase-1, and NLRP3 in the ethanol-treated group. Furthermore, ethanol also caused memory impairment in rats, as measured by behavioural tests. Pretreatment using selected benzimidazole significantly increased the combat of the brain against ethanol-induced oxidative stress. The neuroprotective effects of benzimidazole derivatives were promoted by their free radical scavenging activity, augmentation of endogenous antioxidant proteins (GST, GSH), and amelioration of lipid peroxide (LPO) and other pro-inflammatory mediators. Molecular docking and molecular simulation studies further supported our hypothesis that the synthetic compounds Ca and Cb had an excellent binding affinity with proper bond formation with their targets (TNF-α and NLRP3). Conclusion: It is revealed that these benzimidazole derivatives can reduce ethanol-induced neuronal toxicity by regulating the expression of cytokines, antioxidant enzymes, and the inflammatory cascade.

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Section: Introductionmentioning

confidence: 69%

Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment

Ullah¹,

Kury²,

Althobaiti³

et al. 2022

JIR

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“…Besides, the compound ( 505) increased glutathione (GSH) level, reduced ROS production, and subsequently opened a door for further development to be established as a promising treatment option against Alzheimer’s disease ( Fang et al, 2019 ). Finally, compound 506 exhibited promising neuroprotective role on SH-SY5Y cells by preserving the synaptosomal viability and minimizing GST level compared to the standards melatonin and rasagiline ( Anastassova et al, 2021 ).…”

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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“…Our earlier studies on broad series of benzimidazole-based arylhydrazones [ 31 , 32 , 33 ] outlined the molecular structures bearing the pharmacophores with the most potent multi-target activities in terms of neuroprotection, radical scavenging, and MAO-B inhibition. In particular, the leading structure outlined within a series of benzimidazole hybrids with MAO-B-inhibiting activity was the derivative containing a 2-hydroxy-4-methoxy vanilloid residue ( VII ) [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

New Indole-3-Propionic Acid and 5-Methoxy-Indole Carboxylic Acid Derived Hydrazone Hybrids as Multifunctional Neuroprotectors

et al. 2023

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In light of the known neuroprotective properties of indole compounds and the promising potential of hydrazone derivatives, two series of aldehyde-heterocyclic hybrids combining those pharmacophores were synthesized as new multifunctional neuroprotectors. The obtained derivatives of indole-3-propionic acid (IPA) and 5-methoxy-indole carboxylic acid (5MICA) had good safety profiles: Hemolytic effects < 5% (200 μM) and IC50 > 150 µM were found in the majority of the SH-SY5Y and bEnd3 cell lines. The 2,3-dihydroxy, 2-hydroxy-4-methoxy, and syringaldehyde derivatives of 5MICA exhibited the strongest neuroprotection against H2O2-induced oxidative stress in SH-SY5Y cells and 6-OHDA-induced neurotoxicity in rat-brain synaptosomes. All the compounds suppressed the iron-induced lipid peroxidation. The hydroxyl derivatives were also the most active in terms of deoxyribose-degradation inhibition, whereas the 3,4-dihydroxy derivatives were able to decrease the superoxide-anion generation. Both series of compounds showed an increased inhibition of hMAO-B, with greater expression detected in the 5MICA hybrids. The in vitro BBB model with the bEnd3 cell line showed that some compounds increased the permeability of the endothelial monolayer while maintaining the tight junctions. The combined results demonstrated that the derivatives of IPA and 5MICA showed strong neuroprotective, antioxidant, MAO-B inhibitory activity and could be considered as prospective multifunctional compounds for the treatment of neurodegenerative disorders.

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Evaluation of the combined activity of benzimidazole arylhydrazones as new anti-Parkinsonian agents: monoamine oxidase-B inhibition, neuroprotection and oxidative stress modulation

Cited by 18 publications

References 44 publications

Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment

Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment

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

New Indole-3-Propionic Acid and 5-Methoxy-Indole Carboxylic Acid Derived Hydrazone Hybrids as Multifunctional Neuroprotectors

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