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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 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) | 0.000 | 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".