Antimalarial Agents from Plants: Neocryptolepine Derivatives and Standardised Extracts from Traditional Medicine
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Notice bibliographique
Résumé
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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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle