Correlation study on methoxylation pattern of flavonoids and their heme-targeted antiplasmodial activity
Résumé
A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomimetic MS assay and in vitro antiplasmodial activity on two strains of P. falciparum. Stability of heme adducts was discussed using the dissociation voltage at 50% (DV 50). No correlation was observed between the methoxylation pattern and the antiparasitic activity, either for the 3D7 chloroquine-sensitive or for the W2 chloroquine-resistant P. falciparum strains. However, in each PMF family an increased DV 50 was observed for the derivatives meth-oxylated in position 5. Measurement of intra-erythrocytic hemozoin formation of selected derivatives was performed and hemozoin concentration was inversely correlated with heme-binding affinity. Kaempferol showed no influence on hemozoin formation, reinforcing the hypothesis that this compound may exert in vitro antiplasmodial activity mostly through other pathways. Pentamethoxyquercetin has simultaneously demonstrated a significant biological activity and a strong interaction with heme, suggesting that inhibition of he-mozoin formation is totally or partially responsible for its antiparasitic effect.
Fichier principal
Manuscrit Ortiz and VasquezOcmin BioorgChem 2020.pdf (240.8 Ko)
Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...