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Record W2792009010 · doi:10.1002/jcb.26692

Distinctive inhibition of alkaline phosphatase isozymes by thiazol‐2‐ylidene‐benzamide derivatives: Functional insights into their anticancer role

2018· article· en· W2792009010 on OpenAlexafffund
Syeda Abida Ejaz, Aamer Saeed, Syed Jawad Ali Shah, Abdul Hameed, Joanna Lecka, Jean Sévigny, Jamshed Iqbal

Bibliographic record

VenueJournal of Cellular Biochemistry · 2018
Typearticle
Languageen
FieldMedicine
TopicAlkaline Phosphatase Research Studies
Canadian institutionsUniversité LavalCentre hospitalier de l'Université Laval
FundersFonds de Recherche du Québec - SantéCrohn's and Colitis CanadaCanadian Institutes of Health ResearchHigher Education Commission, Pakistan
KeywordsBenzamideIsozymeAlkaline phosphataseHeLaChemistryCancer cellEnzymeCell cultureDocking (animal)BiochemistryIn vitroPharmacologyCancerCancer researchBiologyStereochemistryMedicineGenetics

Abstract

fetched live from OpenAlex

Abstract In the recent years, the role of alkaline phosphatase (AP) isozymes in the cause of neoplastic diseases such as breast, liver, renal, and bone cancer has been confirmed and, thus they represent a novel target for the discovery of anticancer drugs. In this study different derivatives of thiazol‐2‐ylidene‐benzamide were evaluated for their potential to inhibit alkaline phosphatase (AP) isozymes. Their anticancer potential was assessed using human breast cancer (MCF‐7), bone‐marrow cancer (K‐562), and cervical cancer (HeLa) cell lines in comparison to normal cells from baby hamster kidney BHK‐21. The results suggested that in comparison to other derivatives, compounds 2i , 2e , and 2a showed more sensitivity towards human tissue non‐specific alkaline phosphatase ( h ‐TNAP). Among these, 2″‐chloro‐ N ‐(3‐(4′‐fluorophenyl)‐4‐methylthiazol‐2(3 H )‐ylidene) benzamide ( 2e ) was found as the most potent and selective inhibitor for h ‐TNAP with an IC 50 value of 0.079 ± 0.002 μM. Moreover, a significant correlation was observed between the enzyme inhibition profile and cytotoxic data. The compounds exhibiting maximum anticancer potential also induced maximum apoptosis in the respective cell lines. Furthermore, the DNA interaction studies exhibited the non‐covalent mode of interaction with the herring sperm‐DNA. Molecular docking studies also supported the in vitro inhibitory activity of potent compounds. Our findings suggested that potent and selective inhibitors might be useful candidates for the treatment or prevention of those diseases associated with the higher level of AP. Moreover, the study can be useful for the researcher to explore more molecular mechanisms of such derivatives and their analogues with the exact findings.

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 imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.047
Threshold uncertainty score0.857

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.011
GPT teacher head0.269
Teacher spread0.258 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations3
Published2018
Admission routes2
Has abstractyes

Explore more

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