The local anesthetic activity of <i>Aconitum</i> alkaloids can be explained by their structural properties: a QSAR analysis
Bibliographic record
Abstract
Alkaloids isolated from Aconitum roots exhibit anesthetic effects at peripheral nerves. We performed the present quantitative structure-activity relationship (QSAR) analysis in order to understand the mechanism of action as local anesthetics of 11 Aconitum alkaloids. The alkaloids with the highest anesthetic activity had an aroyl/aroyloxy group at R14 position while the weaker anesthetic alkaloids had the aroyloxy group at R4. The stable compounds exhibited a higher local anesthetic activity than the unstable compounds. In relation to the reactivity indexes of atoms on the aromatic ring, C2' was more reactive while C3' and C5' were less reactive in the compounds with the highest anesthetic activity. Reactivity of N, C1', C4' and C6' was similar between the two groups of alkaloids. The pKa was approximately 7.3 in both groups. The local anesthetic ED50 of alkaloids was significantly inversely related to molecular weight, core-core repulsion energy, steric energy and RI-C2', and directly related to electronic energy, total energy, RI-C5' and to the heat of formation. In conclusion, we identified a set of structural parameters that are related to the local anesthetic activity of Aconitum alkaloids. Our findings are useful to understand the mechanism of action of these alkaloids and to provide a rational for chemical manipulation of the compounds in order to obtain potent derivates with minor toxicity.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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".