Expanding the Alkaline Phosphatase Inhibition, Cytotoxic and Proapoptotic Profile of Biscoumarin‐Iminothiazole and Coumarin‐Triazolothiadiazine Conjugates
Bibliographic record
Abstract
Abstract The present study was aimed to explore the inhibitory potential of coumarin‐hybrids bis‐coumarin‐iminothiazoles (5a‐k) and coumarin‐triazolothiadiazines (10a‐j) against both tissue‐nonspecific alkaline phosphatase (h‐TNAP) and intestinal alkaline phosphatase (h‐IAP) and to link their AP inhibitory potential with possible anti‐proliferative and pro‐apoptotic effect. All investigated compounds were potent inhibitors of h‐TNAP and h‐IAP with several fold better inhibition as compared to standard drugs. In bis‐coumarin‐iminothiazole series, 5f (IC50=0.35±0.01 μM) was found as a lead candidate against h‐TNAP demonstrating a ∼55‐fold higher inhibitory potential as compared to levamisole, whereas, among coumarin‐triazolothiadiazines, 10a (IC50=0.31±0.98 μM) showed ∼62‐fold inhibitory potential. Similarly, compounds 5g and 10d were most potent inhibitors of h‐IAP with an IC50 value of 0.22±0.87 and 0.56±0.04 μM, respectively. The detailed kinetic studies were conducted to probe the mechanism of inhibition. The four potent AP inhibitors 5f, 5h, 10a and 10g also showed maximum anti‐proliferative effect in cancer cells and apoptosis via G2/M phase arrest. 10a and 5f showed maximum cytotoxicity in K‐562 cells (89 and 80%, respectively) with IC50 values of about 2.37 and 7.81 μM, respectively. Our findings suggest these derivatives as potential anti‐cancer candidates with profound anti‐proliferative and pro‐apoptotic behavior along with the ability to block purinergic signaling.
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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) | 0.001 | 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".