Sequential Cytotoxicity: A Theory Evaluated Using Novel 2-[4-(3-Aryl-2-propenoyloxy)phenylmethylene]cyclohexanones and Related Compounds
Bibliographic record
Abstract
Five series of novel compounds were synthesized in order to evaluate the theory of sequential cytotoxicity which seeks to exploit the view that various cancer cells are particularly susceptible to successive attacks by cytotoxic agents. The compounds prepared were various 2-[4-(3-aryl-2-propenoyloxy)phenylmethylene]cyclohexanone s 1 and the related Mannich bases 2. In addition the analogues 3-5 lacking an olefinic bond in the ester group were also synthesized, which were predicted to be less cytotoxic than the compounds of series 1 and 2. The atomic charges at the potential sites for interaction with cellular constituents were determined by molecular modeling calculations. The biodata obtained from murine and human neoplastic cells revealed that the predictions made regarding the viability of the theory were fulfilled in approximately two-thirds of the cases indicating that further investigation of this hypothesis is warranted. In addition, the significant potencies of some of the Mannich bases toward human tumor cell lines, in particular coupled to their selective toxicity toward human leukemic and colon cancer cells, confirms their usefulness in serving as lead molecules for further development. A preliminary investigation into the mode of action of representative compounds revealed their ability to induce apoptosis and inhibit the biosyntheses of ribonucleic acid and proteins.
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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 | 0.000 |
| 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".