Synthesis and Biological Evaluation of Benzimidazole Derivatives as Potential Neuroprotective Agents in an Ethanol-Induced Rodent Model
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".