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Turning a Quinoline-based Steroidal Anticancer Agent into Fluorescent Dye for its Tracking by Cell Imaging

2021· article· en· W3158143408 on OpenAlexaff
René Maltais, Jenny Roy, Donald Poirier

Bibliographic record

VenueACS Medicinal Chemistry Letters · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEstrogen and related hormone effects
Canadian institutionsUniversité Laval
Fundersnot available
KeywordsQuinolineFluorescenceEndoplasmic reticulumColocalizationConfocalChemistryCytotoxic T cellConfocal microscopyFluorescence microscopeCancer cellCellBiophysicsBiochemistryCancerMolecular biologyBiologyCell biologyIn vitroOrganic chemistry

Abstract

fetched live from OpenAlex

RM-581 is an aminosteroid derivative comprised of a steroid core and a quinoline side chain showing potent cytotoxic activity on several types of cancer cells but for which the mechanism of action (MoA) remains to be fully elucidated. The opportunity to turn RM-581 into a fluorescent probe was explored because the addition of a N-dimethyl group was recently reported to induce fluorescence to quinoline derivatives. After the chemical synthesis of the N-dimethyl analogue of RM-581 (RM-581-Fluo), its fluorescent properties, as well as its cytotoxic activity in breast cancer MCF-7 cells, were confirmed. A cell imaging experiment in MCF-7 cells using confocal microscopy then revealed that RM-581-Fluo accumulated into the endoplasmic reticulum (ER) as highlighted by its colocalization with an ER-Tracker dye. This work provides a new tool for RM-581 MoA investigations as well as being a relevant example of a tailor-made quinolone-fluorescent version of a bioactive molecule.

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)0.000
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 score0.013
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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 science0.0000.000
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 head0.005
GPT teacher head0.239
Teacher spread0.234 · 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

Citations22
Published2021
Admission routes1
Has abstractyes

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