Benzodeazaoxaflavin Sirtuin Inhibitors Inhibit <i>Schistosoma mansoni</i> Sirt2 and Cause Phenotypic Changes and Lethality in Schistosomula and Adult Worm Stages
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide Schistosomiasis, a neglected tropical disease caused by trematodes of Schistosoma genus, urgently requires new treatments due to praziquantel’s limited efficacy against juvenile worms as well as the threat of drug resistance. In this study, we evaluated a series of benzodeazaoxaflavin (BDF4)-based compounds as inhibitors of the parasite’s epigenetic enzyme Sm Sirt2. Three compounds, 7 – 9 (MC2346, MC2141, and MC2345), showed activity against both Liberian and Puerto Rican strains of Schistosoma mansoni . The compounds reduced schistosomula and adult worm pair viability, pairing, and egg production, with low cytotoxicity in mammalian cells. These effects were linked to histone H3 hyperacetylation and cytochrome c-mediated apoptosis, confirming Sm Sirt2 as a functional target. These findings support the development of Sm Sirt2 inhibitors as novel antischistosomal agents with therapeutic potential for both curative and preventive applications. Further in vivo studies are warranted to assess their pharmacokinetic and safety profiles.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 0.000 |
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.
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 teacher head, 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".