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This study aimed at identifying antiplasmodial natural products from selected crude extracts from <jats:italic>H. afzelii<\/jats:italic> and <jats:italic>E. calophylloides<\/jats:italic> and to assess their cytotoxicity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The extracts from <jats:italic>H. afzelii<\/jats:italic> and <jats:italic>E. calophylloides<\/jats:italic> were subjected to bioassay-guided fractionation to identify antiplasmodial compounds. The hydroethanol and methanol stem bark crude extracts, fractions and isolated compounds were assessed for antiplasmodial activity against the chloroquine-sensitive 3D7 and multi-drug resistant Dd2 strains of <jats:italic>Plasmodium falciparum<\/jats:italic> using the SYBR green I fluorescence-based microdilution assay. Cytotoxicity of active extracts, fractions and compounds was determined on African green monkey normal kidney <jats:italic>Vero<\/jats:italic> and murine macrophage <jats:italic>Raw<\/jats:italic> 264.7 cell lines using the Resazurin-based viability assay.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The hydroethanolic extract of <jats:italic>H. afzelii<\/jats:italic> stem bark (Hasb<jats:sup>HE<\/jats:sup>) and the methanolic extract of <jats:italic>E. calophylloides<\/jats:italic> stem bark (Ecsb<jats:sup>M<\/jats:sup>) exhibited the highest potency against both <jats:italic>Pf<\/jats:italic>3D7 (EC<jats:sub>50<\/jats:sub> values of 3.32\u2009\u00b1\u20090.15\u2009\u03bcg\/mL and 7.40\u2009\u00b1\u20090.19\u2009\u03bcg\/mL, respectively) and <jats:italic>Pf<\/jats:italic>Dd2 (EC<jats:sub>50<\/jats:sub> of 3.08\u2009\u00b1\u20090.21\u2009\u03bcg\/mL and 7.48\u2009\u00b1\u20090.07\u2009\u03bcg\/mL, respectively) strains. Both extracts showed high selectivity toward <jats:italic>Plasmodium<\/jats:italic> parasites (SI\u2009&gt;\u200913). The biological activity-guided fractionation led to the identification of five compounds (Compounds 1\u20135) from Hasb<jats:sup>HE<\/jats:sup> and one compound (Compound 6) from Ecsb<jats:sup>M<\/jats:sup>. Of these, Compound 1 corresponding to apigenin (EC<jats:sub>50<\/jats:sub><jats:italic>Pf<\/jats:italic>3D7, of 19.01\u2009\u00b1\u20090.72\u2009\u03bcM and EC<jats:sub>50<\/jats:sub><jats:italic>Pf<\/jats:italic>Dd2 of 16.39\u2009\u00b1\u20090.52\u2009\u03bcM), and Compound 6 corresponding to 3,3\u2032-<jats:italic>O<\/jats:italic>-dimethylellagic acid (EC<jats:sub>50<\/jats:sub><jats:italic>Pf<\/jats:italic>3D7 of 4.27\u2009\u00b1\u20090.05\u2009\u03bcM and EC<jats:sub>50<\/jats:sub><jats:italic>Pf<\/jats:italic>Dd2 of 1.36\u2009\u00b1\u20090.47\u2009\u03bcM) displayed the highest antiplasmodial activities. Interestingly, both compounds exhibited negligible cytotoxicity against both <jats:italic>Vero<\/jats:italic> and <jats:italic>Raw<\/jats:italic> 264.7 cell lines with selectivity indices greater than 9.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study led to the identification of two potent antiplasmodial natural compounds, 3,3\u2032-<jats:italic>O<\/jats:italic>-dimethylellagic acid and apigenin that could serve as starting points for further antimalarial drug discovery.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12906-021-03352-9","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T13:02:46Z","timestamp":1624971766000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Identification of 3,3\u2032-O-dimethylellagic acid and apigenin as the main antiplasmodial constituents of Endodesmia calophylloides Benth and Hymenostegia afzelii (Oliver.) 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