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Record W4321166867 · doi:10.1021/acs.jnatprod.2c01041

Using a Bioactive <i>Eremophila</i>-Derived Serrulatane Scaffold to Generate a Unique Carbamate Library for Anti-infective Evaluations

2023· article· en· W4321166867 on OpenAlexfundno aff
Chen Zhang, Kah Yean Lum, Aya C. Taki, Robin B. Gasser, Joseph J. Byrne, Luis J. Montaner, Ian Tietjen, Vicky M. Avery, Rohan A. Davis

Bibliographic record

VenueJournal of Natural Products · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicTraditional and Medicinal Uses of Annonaceae
Canadian institutionsnot available
FundersNational Institute of Neurological Disorders and StrokeNational Institute on Drug AbuseNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteAustralian Research CouncilCanadian Institutes of Health ResearchGriffith UniversityUniversity of MelbourneNational Institute of Allergy and Infectious DiseasesPhiladelphia Foundation
KeywordsCarbamateStereochemistryTerpenoidBioactive compoundAnthelminticPlasmodium falciparumChemistryIC50Natural productBiologyCombinatorial chemistryOrganic chemistryBiochemistryIn vitro

Abstract

fetched live from OpenAlex

The known Eremophila microtheca -derived diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid ( 1 ) was targeted for large-scale purification, as this bioactive plant compound has proven to be an attractive scaffold for semisynthetic studies and subsequent library generation. Compound 1 was converted to a selectively protected trimethyl derivative, 3-hydroxy-7,8-dimethoxyserrulat-14-en-19-oic acid methyl ester ( 2 ), using simple and rapid methylation conditions. The resulting scaffold 2 was reacted with a diverse series of commercially available isocyanates to generate an 11-membered carbamate-based library. The chemical structures of the 11 new semisynthetic analogues were fully characterized by spectroscopic and spectrometric analysis. All natural products and semisynthetic compounds were evaluated for their anthelmintic, antimalarial, and anti-HIV activities. Compound 3 was shown to elicit the greatest antiplasmodial activity of all compounds tested, with IC 50 values of 4.6 and 11.6 μM against Plasmodium falciparum 3D7 and Dd2, respectively. Compound 11 showed the greatest inhibition of development to fourth-stage Haemonchus contortus larvae (L4) and induction of a skinny ( Ski ) phenotype (67.5% of nematodes) at 50 μM. Compound 7, which inhibited 59.0% of HIV production at 100 μg/mL, was the carbamate analogue that displayed the best antiviral activity.

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

Direct model labels (unvalidated)

Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.

Model armCategoriesStudy designConfidence
gemmano category
Domain: not available · Genre: Empirical
About the Canadian research system: no · About a Canadian topic: no
Bench or experimentalhigh
gptno category
Domain: not available · Genre: Empirical
About the Canadian research system: no · About a Canadian topic: no
Bench or experimentalhigh
models agreeAgreement compares identical category sets and study designs across arms.

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 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 score0.010
Threshold uncertainty score0.514

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 head0.042
GPT teacher head0.324
Teacher spread0.282 · 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

Labeled directly by 2 models reading the full record.

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

Citations4
Published2023
Admission routes1
Has abstractyes

Explore more

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