Synthetic analogs of the marine natural product hemiasterlin: Optimization and discovery of E7974, a novel and potent antitumor agent
Bibliographic record
Abstract
1213 A series of 13 anthrapyrazole (AP) compounds that were analogs of piroxantrone and losoxantrone were synthesized. Three-dimensional quantitative structure-activity analyses (3D-QSAR) were carried out on the AP compounds using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) in order to determine the factors affecting the cell growth inhibitory (CHO, DZR, K562 and K/VP.5 cells), DNA binding (ΔTm) and inhibition of DNA topoisomerase II decatenation catalytic activity. Conformational analysis of all analogs was first performed with the CONFORT module implemented in SYBYL to identify the global minimum energy conformation. The most active compound, AP10, was then used as the template molecule. Steric and electrostatic fields were determined in CoMFA and three additional fields (hydrophobic, hydrogen donor and hydrogen acceptor) were determined in CoMSIA. Both CoMFA and CoMSIA analysis of the biological properties yielded statistically significant models upon partial least squares analysis. The information obtained from CoMFA and CoMSIA 3D-contour maps is to be used to predict the activity of new anthrapyrazoles with increased activity. Support: CIHR and a Canada Research Chair in Drug Development
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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) | 0.002 | 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".