Targeting the intra-erythrocytic life cycle of Plasmodium falciparum unveils antimalarial drug discovery starting points from Drymaria cordata and Macaranga monandra

Kamche Aubin Youbi; Mariscal Brice Tchatat Tali; Vincent Ngouana; Diana Sandra Wendji Monkam; Hassan Souleyman; Yanick Kevin Melogmo Dongmo; Kevine Johane Jumeta Dongmo; Olga Nana; David Woutouoba Ntieche; Darline Dize; Cedric Derick Jiatsa Mbouna; Patrick Valere Tsouh Fokou; Fabrice Fekam Boyom

doi:10.1016/j.jep.2025.120518

Targeting the intra-erythrocytic life cycle of Plasmodium falciparum unveils antimalarial drug discovery starting points from Drymaria cordata and Macaranga monandra

J Ethnopharmacol. 2026 Jan 10:354:120518. doi: 10.1016/j.jep.2025.120518. Epub 2025 Sep 1.

Authors

Affiliations

¹ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Advanced Research & Health Innovation Hub, P.O. Box 20133, Yaoundé, Cameroon. Electronic address: akyoubi@yahoo.com.
² Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Advanced Research & Health Innovation Hub, P.O. Box 20133, Yaoundé, Cameroon. Electronic address: brice.tchatat@facsciences-uy1.cm.
³ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Department of Pharmaceutical Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Dschang, P.O. Box 96, Dschang, Cameroon. Electronic address: ngouanavincent@yahoo.fr.
⁴ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: dianawendji@gmail.com.
⁵ Faculty of Human Health Sciences (FSSH), Laboratory of Research, Diagnostics and Scientific Expertise (LaboREDES), Parasitology Unit, University of N'Djamena, P.O. Box 1117, N'Djamena, Chad. Electronic address: souleymanrahamahassan@gmail.com.
⁶ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: melogmoyanne@gmail.com.
⁷ Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: jumetakevine@yahoo.fr.
⁸ Department of Chemistry, Faculty of Science, University of Ngaoundéré, P.O. Box 454, Ngaoundéré, Cameroon. Electronic address: ndounkeuolga@gmail.com.
⁹ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: dntieche@yahoo.com.
¹⁰ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: darline.dize@yahoo.fr.
¹¹ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. Electronic address: cedrickjiatsa@yahoo.com.
¹² Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Advanced Research & Health Innovation Hub, P.O. Box 20133, Yaoundé, Cameroon; Department of Biochemistry, Faculty of Science, University of Bamenda, P.O. Box 39, Bambili, Cameroon. Electronic address: ptsouh@gmail.com.
¹³ Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon; Advanced Research & Health Innovation Hub, P.O. Box 20133, Yaoundé, Cameroon. Electronic address: fabrice.boyom@fulbrightmail.org.

PMID: 40902808
DOI: 10.1016/j.jep.2025.120518

Abstract

Ethnopharmacological relevance: Drymaria cordata and Macaranga monandra are two medicinal plants traditionally used in Cameroon to treat malaria, but their scientific validation remains unclear.

Aim of the study: To validate the antiplasmodial action of extracts and fractions derived from Drymaria cordata and Macaranga monandra.

Materials and methods: Aqueous, methanolic, ethanolic, and hydroethanolic extracts of D. cordata (whole plant) and M. monandra (bark) were prepared by maceration followed by liquid-liquid partition of actives. Extracts and fractions were screened against chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) strains of P. falciparum, while selectivity was determined on Vero cells. Stage-specific analysis and killing dynamics of potent fractions were profiled, complemented with UHPLC-MS analysis coupled to in silico prediction of pharmacokinetics of identified metabolites.

Results: D. cordata ethanolic extract showed moderate activity (IC₅₀PfDd2: 18.9 μg/mL; IC₅₀Pf3D7: 24.51 μg/mL), while all four M. monandra extracts exhibited good activity (IC₅₀ < 8 μg/mL). The methanolic bark extract (MMBME) was highly potent and selective (IC₅₀PfDd2: 2.46 μg/mL, SI > 203; IC₅₀Pf3D7: 1.02 μg/mL, SI > 487). Fractionation yielded two active fractions from MMBME: F2 (IC₅₀PfDd2: 0.60 μg/mL, IC₅₀Pf3D7: 3.42 μg/mL) and F3 (IC₅₀PfDd2: 0.92 μg/mL, IC₅₀Pf3D7: 2.46 μg/mL). Fractions F2 and F3 arrested ring-stage development, lysed trophozoite-infected red blood cells, and blocked merozoite egress. UHPLC-MS analysis identified 17 metabolites in fractions F2 and F3, including fatty acyls, flavonoids, phenols, terpenes, and coumarins. Lecanoric acid was predicted as a promising antimalarial candidate.

Conclusions: Macaranga monandra bark fractions F2 and F3 are potent sources of antiplasmodial compounds targeting multiple asexual blood stages (ABS).

Keywords: Drymaria cordata; In silico prediction; In vitro efficacy; Macaranga monandra; Pharmacodynamics; Plasmodium falciparum.

MeSH terms

Animals
Antimalarials* / isolation & purification
Antimalarials* / pharmacology
Cameroon
Chlorocebus aethiops
Drug Discovery
Erythrocytes* / drug effects
Erythrocytes* / parasitology
Life Cycle Stages / drug effects
Plant Extracts* / isolation & purification
Plant Extracts* / pharmacology
Plasmodium falciparum* / drug effects
Plasmodium falciparum* / growth & development
Vero Cells

Substances

Antimalarials
Plant Extracts