A Novel Class of Orally Bioavailable Phenylglycine–Benzoxaborole Conjugates with Antimalarial Activity and Potentially Novel Mechanism of Action
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide A new class of benzoxaboroles with a phenylglycine appendage was found to display in vitro blood stage activity against the human malaria parasite Plasmodium falciparum ( Pf ). Structure–activity relationship studies of the starting hit compound 3 resulted in compounds active against Pf NF54 drug-sensitive and Pf K1 drug-resistant strains with an in vitro antiplasmodium IC 50 < 0.4 μM, selectivity over mammalian cell-lines (selectivity index > 47) and high aqueous solubility (160 to >200 μM). Selected compounds showed good in vitro metabolic stability when incubated with human, rat, and mouse liver microsomes and showed no cross-resistance against barcoded mutant lines. Two frontrunner compounds, 6 and 7, were dosed orally at 50 mg·kg –1 using a standard quadrupole dosing regimen in a P. berghei mouse infection model and showed encouraging in vivo efficacy. This work identifies a promising new class of phenylglycine-based benzoxaboroles, which warrants further medicinal chemistry optimization.
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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) | 0.002 | 0.001 |
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".