Antimalarial Agents from Plants: Neocryptolepine Derivatives and Standardised Extracts from Traditional Medicine
Bibliographic record
Abstract
Plants are still an important resource for the discovery of new drugs, such as new antimalarial agents. In search for novel antimalarial compounds, we focused on neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline), one of the minor alkaloids of Cryptolepis sanguinolenta, a plant used in traditional medicine in Central and West Africa. A series of chloro- and aminoalkylamino-substituted neocryptolepine derivatives were synthesized and evaluated as antiplasmodial agents. The evaluation included cytotoxicity (MRC5 cells), inhibition of β-hematin formation and DNA-interactions (DNA/methyl green assay). Introduction of aminoalkylamino chains increased the antiplasmodial activity of the neocryptolepine core substantially. The most active compounds showed antiplasmodial activities in the nM range. Nevertheless, some compounds that were selected for in vivo evaluation in infected mice were not sufficiently active, or toxic to the animals. A different approach to develop antimalarial drugs from nature is the standardisation of plant extracts with a proven efficacy used in traditional medicine. Nauclea pobeguinii (Rubiaceae) is a tree from which the bark is widely used in African traditional medicine against malaria-like symptoms. Alkaloids such as the major compound strictosamide are expected to be responsible for the activity. An HPLC method was developed and validated for the quantification of strictosamide in an 80% EtOH extract of the stem bark of N. pobeguinii. This extract, containing 5.6% (w/w) strictosamide, was evaluated in vivo in the Plasmodium berghei mouse model in a suppressive treatment regimen. It was orally dosed (PO) at 300 mg/kg 2 ×/day during 5 consecutive days. Another group was treated intraperitoneally (IP) at 50 mg/kg using the same dosing regimen. Treatment with the crude extract, either after oral or intraperitoneal dosing, resulted in moderate depression of parasitaemia during dosing, however quickly followed by a full relapse (mean survival time = about 13 days). At termination of the experiment at day 21, a single survivor in the PO group was apparently cured (no parasitaemia), the single survivor in the IP group showed high parasitaemia and was in a moribund state. It can be concluded that the crude extract of N. pobeguinii has slight antimalarial potential when administered orally in a suppressive dosing regimen of 2 × 5 days at 300 mg/kg. Longer treatment may be necessary.
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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 | 0.001 | 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 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".