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Record W3120570340 · doi:10.1021/acschemneuro.0c00659

Synthesis and Biological Evaluation of Benzimidazole Derivatives as Potential Neuroprotective Agents in an Ethanol-Induced Rodent Model

2021· article· en· W3120570340 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueACS Chemical Neuroscience · 2021
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsNeuroprotectionNeurodegenerationNeuroinflammationOxidative stressPharmacologyProinflammatory cytokineAcetamideChemistryBenzimidazoleReactive oxygen speciesBiochemistryBiologyMedicineInflammationImmunologyInternal medicineDisease

Abstract

fetched live from OpenAlex

Alzheimer’s disease (AD) is the most devastating and progressive neurodegenerative disease in middle to elder aged people, which can be exacerbated by lifestyle factors. Recent longitudinal studies demonstrated that alcohol consumption exacerbates memory impairments in adults. However, the underlying mechanism of alcohol-induced memory impairment is still elusive. The increased cellular manifestation of reactive oxygen species (ROS) and the production of numerous proinflammatory markers play a critical role in the neurodegeneration and pathogenesis of AD. Therefore, reducing neurodegeneration by decreasing oxidative stress and neuroinflammation may provide a potential therapeutic roadmap for the treatment of AD. In this study, eight new benzimidazole acetamide derivatives (FP1, FP2, FP5–FP10) were synthesized and characterized to investigate its neuroprotective effects in ethanol-induced neurodegeneration in a rat model. Further, three derivatives (FP1, FP7, and FP8) were selected for in vivo molecular analysis based on preliminary in vitro antioxidant screening assay. Molecular docking analysis was performed to assess the affinity of synthesized benzimidazole acetamide derivatives against selected proinflammatory targets (TNF-α, IL-6). Biochemical analysis revealed elevated expression of neuroinflammatory markers (TNF-α, NF-κB, IL-6, NLRP3), increased cellular oxidative stress, and reduced antioxidant enzymes in ethanol-exposed rats brain. Notably, pretreatment with new benzimidazole acetamide derivatives (FP1, FP7, and FP8) significantly modulated the ethanol-induced memory deficits, oxidative stress, and proinflammatory markers (TNF-α, NF-κB, IL-6, NLRP3) in the cortex. The multipurpose nature of acetamide containing benzimidazole nucleus and its versatile affinity toward numerous receptors highlight its multistep targeting potential. These results indicated the neuroprotective potential of benzimidazole acetamide derivatives (FP1, FP7, and FP8) as novel therapeutic candidates in ethanol-induced neurodegeneration which may partially be due to inhibition of the neuroinflammatory–oxidative stress vicious cycle.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.006
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.214
Threshold uncertainty score0.811

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.006
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.160
GPT teacher head0.344
Teacher spread0.184 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it