2. Academic Validation
  3. Eschweilenol C and subfractions from Terminalia plants disrupt haemoglobin metabolism, inhibiting Plasmodium falciparum growth at rings and trophozoite stages

Eschweilenol C and subfractions from Terminalia plants disrupt haemoglobin metabolism, inhibiting Plasmodium falciparum growth at rings and trophozoite stages

  • Malar J. 2025 Nov 24;24(1):422. doi: 10.1186/s12936-025-05445-z.
Mariscal Brice Tchatat Tali 1 2,  Cedric Derick Jiatsa Mbouna 3,  Aafreen Zehra 4,  Steven Collins Njonte Wouamba 5,  Guy Paulin Kemayou Mouthe 5,  Aubin Youbi Kamche 3 6,  Darline Dize 3 7,  Simeon Fogue Kouam 5,  Boniface Pone Kamdem 3 8,  Jean Claude Tchouankeu 5,  Feroz Khan 4,  Fabrice Fekam Boyom 9 10
Affiliations

Affiliations

  • 1 Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon. [email protected].
  • 2 Advanced Research & Health Innovation Hub, P.O. Box 20133, Yaoundé, Cameroon. [email protected].
  • 3 Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon.
  • 4 Technology Dissemination & Computational Biology Division, CSIR-Central Institute of Medicinal & Aromatic Plants, P.O.-CIMAP, Kukrail Picnic Spot Road, Lucknow, 226015, Uttar Pradesh, India.
  • 5 Department of Chemistry, Higher Teacher Training College, University of Yaoundé 1, P. O. Box 47, Yaoundé, Cameroon.
  • 6 Advanced Research & Health Innovation Hub, P.O. Box 20133, Yaoundé, Cameroon.
  • 7 African Institute of Biomedical Science and Technology, Harare, Zimbabwe.
  • 8 Department of Agriculture, Livestock and Fisheries Science, Higher Institute of Agriculture, Forestry, Water and Environment (HIAFWE), University of Ebolowa (UEbwa), P.O. Box 755, Ebolowa, Cameroon.
  • 9 Antimicrobial and Biocontrol Agents Unit, Laboratory for Phytobiochemistry and Medicinal Plants Studies, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon. [email protected].
  • 10 Advanced Research & Health Innovation Hub, P.O. Box 20133, Yaoundé, Cameroon. [email protected].
PMID: 41286749 DOI: 10.1186/s12936-025-05445-z
Abstract

Background: The rising prevalence of artemisinin-resistant malaria parasites in Africa underscores the urgent demand for new and effective therapeutic options. Historically, natural products have demonstrated significant anti-Plasmodium efficacy, indicating their potential as a source for malaria drug discovery. Extracts and fractions from Terminalia ivorensis and Terminalia brownii previously exhibited promising anti-Plasmodium potency; however, a thorough assessment of their pharmacodynamics across all asexual blood stages of Plasmodium falciparum and elucidation of their mode of action remains to be conducted. Products from the active fractions of T. ivorensis (TiWEa) and T. brownii (TbMMeOH:Ea) were investigated throughout the asexual-blood and sexual stages of P. falciparum, focusing on their mechanism of inhibition and interaction with some key targets of haemoglobin metabolism.

Methods: Both active fractions (TiWEa and TbMMeOH:Ea) were fractionated by column chromatography, and the chemical structures of the isolated compound were elucidated through physical and spectroscopic techniques. The resulting compound and subfractions were screened in vitro against P. falciparum strains (Dd2, 3D7, and Dd2-GNF156), stage V gametocytes, and mammalian cells. The pharmacodynamics (stage-specific analysis and killing kinetics) of potent inhibitors were assessed and complemented by the effect on haemozoin formation. The molecular interaction between the potent compound and the two target Enzymes was investigated through molecular docking.

Results: The fractionation of TiWEa yielded five subfractions (Ti01, Ti02, Ti03, Ti04, Ti05), while TbMMeOH:Ea yielded three subfractions (Tb01, Tb02, Tb03) along with one compound (01) characterized as eschweilenol C. All Subfractions demonstrated good activity on susceptible and multidrug-resistant strains of P. falciparum (3D7 and Dd2) with an IC50 ranging from 0.15 to 5.73 µg/ml. eschweilenol C equally displayed an IC50 of 490.74 and 379.20 nM, respectively, on PfDd2 and Pf3D7. Two top hits subfractions (Ti03; Ti04) from TiWEa and eschweilenol C from TbMMeOH:Ea exhibited a perfect antiplasmodial profile (IC50 < 1 µg/ml); good selectivity (SI > 10) and demonstrated no spontaneous loss of efficacy when tested against mutant resistant strain (PfDd2-GNF156) of P. falciparum. Ti03, Ti04, and eschweilenol C reduced haemozoin production, exhibited killing activity on ring and trophozoite stages and showed significant binding affinity to PfM1AAP and PfM17LAP.

Conclusion: This study identifies eschweilenol C as a promising candidate for malaria drug discovery efforts and its significance for further exploration in the context of the emergence of artemisinin-resistant parasites in Africa.

Keywords

Eschweilenol C; Malaria; Molecular docking; Pharmacodynamics; Pharmacokinetics.

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