Modular Synthesis of 1,2- and 1,1′-Disubstituted Ferrocenyl Carbohydrate Chloroquine and Mefloquine Conjugates as Potential Antimalarial Agents
Why this work is in the frame
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Bibliographic record
Abstract
The modular synthesis of novel organometallic antimalarials based on a 1,2- or 1,1′-disubstituted ferrocene scaffold ( 10 and 11 ) is presented. Ferrocenes were substituted via an ether linker with either 7-chloroquinoline or 2,8-bis(trifluoromethyl)quinoline, as a chloroquine or mefloquine derivative, respectively. Diisopropylidene-protected 6-amino-6-deoxyglucofuranose ( 18 ) or 6-amino-6-deoxygalactopyranose ( 21 ) was coupled via reductive amination to yield the target conjugates 24 – 27 and 30 . Yields could be substantially increased using a microwave reactor instead of conventional heating, which reduced the reaction time as well. After complete characterization these novel trifunctional conjugates were examined for their antiplasmodial activity in a chloroquine-susceptible (CQS) strain of Plasmodium falciparum (D10) and a chloroquine-resistant (CQR) strain (Dd2). The determined IC 50 values were in the low micromolar range. Introduction of the carbohydrate led to an increase in activity (>200 μM ( 16, D10) to 1.2 μM ( 24, D10)). The best activity was measured for 26 in Dd2 (IC 50 = 0.77 μM). Resistance indices (RI) for all measured compounds were <1, indicating a higher activity in the chloroquine-resistant Dd2 strain in comparison to the chloroquine-susceptible D10 strain (RI = 0.93 for 24, RI = 0.15 for 25 ).
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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) | 0.001 | 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 it