Bio-guided investigation of nine Niger's ethnomedicinal plants reveals nature-derived antimalarial chemical pharmacophores for drug discovery.

Malaria is a significant concern due to the emergence of artemisinin-resistant parasites. This study aims to unveil the selective inhibitory potential of extracts and derivatives of some Niger's plants against Plasmodium falciparum. Plant extracts were screened on chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) P. falciparum strains using the SYBR Green method, followed by bio-guided fractionation of active extracts. Bio-guided method was used for the isolation. Resazurin-based and hemoglobin quantification assays were used to assess the selectivity on normal RAW cells and erythrocytes, respectively. Among the 27 extracts, five exhibited pronounced activity (IC50 < 5 µg/mL) against multidrug-resistant (PfDd2) and three against sensitive (Pf3D7) strains of P. falciparum. The methanolic extract from Phyllanthus pentandrus displayed the most promising activity the most active on both strains (IC50PfDd2 = 1.85 µg/mL and IC50Pf3D7 = 4.25 µg/mL). Its fractionation led to five fractions, among which the ethyl acetate fraction was the most active (IC50PfDd2 = 3.10 µg/mL). Four compounds were isolated from the ethyl acetate fraction: kaempferol, quercetin, gallic acid, and quercetin-3-O-rutinoside. Active extracts and fractions showed good selectivity on normal RAW cells and erythrocytes. This study validates the medicinal use of Niger ethnomedicine for the treatment of malaria.