Effect of cyclooxygenase-2 (COX-2) inhibitors on prostate cancer cell proliferation.
Bibliographic record
Abstract
BACKGROUND: The tricyclic cyclooxygenase-2 (COX-2) inhibitors celecoxib and rofecoxib exhibit different magnitudes of antiproliferative activity against the human prostate cancer cell lines LNCaP and PC-3. We investigated the correlation between the COX-2 inhibitory potencies, antiproliferative activities and the nature of the central ring system of novel tricyclic COX-2 inhibitors belonging to the diarylcycloalkyl and diarylheterocyclic classes possessing a central 3-membered cyclopropyl (1 and 2), a 5-membered isoxazoline (3), an isoxazole (4) or 2-(5H) furanone (5), and a 6-membered pyran-2-one (6a-c) ring system. MATERIALS AND METHODS: Novel tricyclics were synthesized and evaluated in vitro for their COX-1/COX-2 inhibitory activities and their abilities to inhibit cell proliferation in prostate (AT3B-1, PC-3 and LNCaP) and breast (MCF-7) cancer cell lines. A molecular modeling study was carried out to characterize the electronic nature of the central ring systems of the novel tricyclic COX-2 inhibitors. RESULTS: The isoxazoline (3), which exhibited excellent COX-2 inhibitory potency and selectivity, showed growth inhibition in all the cell lines tested with IC50 values of 349 microM (AT3B-1), 378 microM (PC-3), 100 microM (LNCaP) and 200 microM (MCF-7), respectively. The rofecoxib analog (5) and 6-membered pyran-2-ones (6a-c) showed weak inhibition (MCF-7, AT3-B-1 and PC-3) inspite of possessing good COX-2 inhibitory potencies and selectivities. CONCLUSION: This study demonstrates that the antiproliferative activity profiles exhibited by the novel tricyclic COX-2 inhibitors is dependent on the electronic nature of the central ring system and is independent of their COX-2 inhibitory potencies and selectivities. Accordingly, the 2,3-dimethyl-5-(4-methylsulfonylphenyl)-4-phenyl-4-isoxazoline (3), which possesses an electron rich central 5-membered isoxazole ring, could serve as a lead compound to develop novel drugs to treat prostate cancer.
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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".