Benzofuran and Benzo[<i>b</i>]thiophene‐2‐Carboxamide Derivatives as Modulators of Amyloid Beta (Aβ42) Aggregation
Bibliographic record
Abstract
A group of N-phenylbenzofuran-2-carboxamide and N-phenylbenzo[b]thiophene-2-carboxamide derivatives were designed and synthesized as a novel class of Aβ42 aggregation modulators. In the thioflavin-T based fluorescence aggregation kinetics study, compounds 4 a, 4 b, 5 a and 5 b possessing a methoxyphenol pharmacophore were able to demonstrate concentration dependent inhibition of Aβ42 aggregation with maximum inhibition of 54 % observed for compound 4 b. In contrast, incorporation of a 4-methoxyphenyl ring in compounds 4 d and 5 d led to a significant increase in Aβ42 fibrillogenesis demonstrating their ability to accelerate Aβ42 aggregation. Compound 4 d exhibited 2.7-fold increase in Aβ42 fibrillogenesis when tested at the maximum concentration of 25 μM. These results were further confirmed by electron microscopy studies which demonstrates the ability of compounds 4 a, 4 b, 4 d, 5 a, 5 b and 5 d to modulate Aβ42 fibrillogenesis. Compounds 5 a and 5 b provided significant neuroprotection to mouse hippocampal neuronal HT22 cells against Aβ42-induced cytotoxicity. Molecular docking studies suggest that the orientation of the bicyclic aromatic rings (either benzofuran or benzo[b]thiophene) plays a major role in moderating their ability to either inhibit or accelerate Aβ42 aggregation. Our findings support the application of these novel derivatives as pharmacological tools to study the mechanisms of Aβ42 aggregation.
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.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".