Synthesis, in vitro and in silico studies of inhibitory activity towards <i>α</i>-amylase of <i>bis</i>-azole scaffolds linked by an alkylsulfanyl chain
Bibliographic record
Abstract
Twelve new α,ω-bis[(3,5-dimethylpyrazol-4-yl)methylsulfanyl]alkanes linked by alkyl, diethyl sulfide, and triethyl dioxide spacers were prepared by the multicomponent reaction of acetylacetone, formaldehyde, α,ω-dithiols, and monosubstituted hydrazines. Testing of these products for inhibition of α-amylase enzyme in vitro showed that bis(N-methylpyrazolylmethylsulfanyl)ethane 4a inhibits the enzyme by the competitive mechanism. Meanwhile, the water-soluble adduct of bis(isoxazolylmethylsulfanyl)ethane 2 with HCl (2·HCl) is a noncompetitive inhibitor. The molecular docking results attest to high complementarity between the test molecules and the enzymes such as α-amylases from Aspergillus niger and human pancreas. Bis-pyrazole compounds 1, 1·HCl, and 4a and bis-isoxazole compounds 2 and 2·HCl positioned in the active site of both α-amylases form two closely spaced clusters. For all cases, the bioactive conformations of the modeled ligands were identified, demonstrating high affinity of the bis-azoles (1, 1·HCl, 2, 2·HCl, 4a) to the enzymes. Hydrogen bonds stabilizing their position in both α-amylases active sites were identified.
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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) | 0.001 | 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".