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Record W4361001386 · doi:10.21203/rs.3.rs-2701574/v1

A specific dispiropiperazine derivative that arrests cell cycle, induces apoptosis, necrosis and DNA damage

2023· preprint· en· W4361001386 on OpenAlexafffund
Victor Liu, Wai-Ming Li, Jack Lofroth, Mehreen Zeb, Brian O. Patrick, Tina M. Bott, Chow H. Lee

Bibliographic record

VenueResearch Square · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer therapeutics and mechanisms
Canadian institutionsMacEwan UniversityUniversity of British ColumbiaUniversity of Northern British Columbia
FundersNatural Sciences and Engineering Research Council of CanadaUniversity of Northern British Columbia
KeywordsApoptosisCell cycleProgrammed cell deathCell cycle checkpointMitosisCancer cellG1 phaseFlow cytometryMolecular biologyAcenaphtheneNecrosisMitotic catastropheCell cultureDNA damageCell growthViability assayCancer researchChemistryBiologyCancerCell biologyDNABiochemistryGenetics

Abstract

fetched live from OpenAlex

Abstract Dispiropiperazine compounds are a class of molecules known to confer biological activity, but those that have been studied as cell cycle regulators are few in number. Here, we report the characterization and synthesis of two dispiropiperazine derivatives: the previously synthesized spiro[2’,3]-bis(acenaphthene-1’-one)perhydrodipyrrolo-[1,2-a:1,2-d]-pyrazine (SPOPP-3, 1 ), and its previously undescribed isomer, spiro[2’,5’]-bis(acenaphthene-1’-one)perhydrodipyrrolo-[1,2-a:1,2-d]-pyrazine (SPOPP-5, 2 ). SPOPP-3 ( 1 ), but not SPOPP-5 ( 2 ), was shown to have anti-proliferative activity against a panel of 18 human cancer cell lines with IC 50 values ranging from 0.63-13 µM. Flow cytometry analysis revealed that SPOPP-3 ( 1 ) was able to arrest cell cycle at the G2/M phase in SW480 human cancer cells. Western blot analysis further confirmed the cell cycle arrest is in the M phase. In addition, SPOPP-3 ( 1 ) was shown to induce apoptosis, necrosis, and DNA damage as well as disrupt mitotic spindle positioning in SW480 cells. These results warrant further investigation of SPOPP-3 ( 1 ) as a novel anti-cancer agent, particularly for its potential ability to sensitize cancer cells for radiation-induced cell death, enhance cancer immunotherapy, overcome apoptosis-related drug resistance and for possible use in synthetic lethality cancer treatments.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.035
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.002
Research integrity0.0010.001
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 head0.085
GPT teacher head0.368
Teacher spread0.284 · 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.

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

Citations1
Published2023
Admission routes2
Has abstractyes

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