The potential of quinoline derivatives for the treatment of Toxoplasma gondii infection
Bibliographic record
Abstract
Here we reported our investigation, as part of our drug repositioning effort, on anti-Toxoplasma properties of newly synthesized quinoline compounds. A collection of 4-aminoquinoline and 4-piperazinylquinoline analogs have recently been synthesized for use in cancer chemotherapy. Some analogs were able to outperform chloroquine, a quinoline derivative drug which is commonly used in the treatment of malaria and other parasitic infections. Herein 58 compounds containing one or two quinoline rings were examined for their effectiveness as potential anti-Toxoplasma compounds. Of these 58 compounds, 32 were efficient at inhibiting Toxoplasma growth (IC50<100 μM). Five compounds with single and simple quinoline rings exhibited similar cLogP values of ∼2 and IC50 values between 5 and 6 μM, with one exception of 8-hydroxyquinoline whose IC50 value was 213 nM. The addition of one hydroxyl group at position 8 caused a 40-fold increase in the inhibitory effect of quinoline. A significant improvement in anti-Toxoplasma effect among quinoline derivatives was detected in B11, B12, B23, and B24, whose structures carry two quinoline rings, and their resultant cLogP values are ⩾7. Among these compounds, B23 was the most effective compound with IC50 value of 425±35 nM, and TI value of 4.9. It was also noted that compounds with at least one quinoline ring, displaying anti-Toxoplasma effects were capable of causing the disappearance of the apicoplast, a plastid-like organelle. When treated with quinoline, 8-hydroxyquinoline or B23, 40-45% of the parasites lost their apicoplasts. Our findings recapitulate the properties of quinoline derivatives in diminishing apicoplast. This could aid further investigations of anti-parasitic treatments specific to Apicomplexan. More importantly, B12 and B23 which harbor superior anti-cancer properties than chloroquine, have effective anti-Toxoplasma activity. These compounds therefore have significant potential for future development of chemotherapeutic agents for patients suffering from breast cancers and parasitic infection.
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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 | 0.000 |
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 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".