{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:24:42Z","timestamp":1788531882009,"version":"build-2803163510"},"reference-count":89,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010034","name":"Walailak University","doi-asserted-by":"publisher","award":["WU68259"],"award-info":[{"award-number":["WU68259"]}],"id":[{"id":"10.13039\/501100010034","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010034","name":"Walailak University","doi-asserted-by":"publisher","award":["WU-CIA-06407\/2025"],"award-info":[{"award-number":["WU-CIA-06407\/2025"]}],"id":[{"id":"10.13039\/501100010034","id-type":"DOI","asserted-by":"publisher"}]},{"award":["WU68259"],"award-info":[{"award-number":["WU68259"]}],"id":[{"id":"https:\/\/ror.org\/04b69g067","id-type":"ROR","asserted-by":"publisher"}]},{"award":["WU-CIA-06407\/2025"],"award-info":[{"award-number":["WU-CIA-06407\/2025"]}],"id":[{"id":"https:\/\/ror.org\/04b69g067","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Malaria is a life-threatening global disease, and despite artemisinin-based combination therapies (ACTs) as first-line treatment, emerging drug-resistant Plasmodium strains necessitate novel antimalarial agents. This study investigated the antiplasmodial potential of Eurycoma harmandiana Pierre (EH) root extract, a medicinal plant closely related to Eurycoma longifolia Jack (EL). The extract and its derived compounds were evaluated using in vitro antiplasmodial and cytotoxicity assays. The active compounds were further investigated by parasite morphological analysis, molecular docking against quadruple-mutant Plasmodium falciparum dihydrofolate reductase (qmPfDHFR), molecular dynamics (MD) simulations, and in silico prediction of drug-likeness, pharmacokinetic properties, and toxicity. The ethanolic extract exhibited potent antiplasmodial activity (IC50 = 0.51 \u00b5g\/mL) with low cytotoxicity (CC50 = 31.68 \u00b5g\/mL) and a high selectivity index (SI = 62.11). Quassinoids showed the strongest activity (IC50 = 0.13\u20130.87 \u00b5M), whereas alkaloids displayed good to moderate activity. The extract and two promising bioactive quassinoids, eurycomanone (1) and glaucarubolone (5), disrupted intraerythrocytic parasite development. Molecular docking and MD simulations demonstrated that glaucarubolone (5) exhibited favorable predicted interactions with qmPfDHFR, along with favorable predicted drug-like properties, pharmacokinetic profiles, and low toxicity. This study provides the first report of the antiplasmodial activity of Eurycoma harmandiana, highlighting it as a promising alternative source of bioactive compounds against Plasmodium parasites. Glaucarubolone (5) may represent a promising scaffold for further investigation toward the development of novel antimalarial agents.<\/jats:p>","DOI":"10.3390\/ijms27177892","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:50:44Z","timestamp":1788529844000},"page":"7892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antiplasmodial Compounds from Eurycoma harmandiana Pierre and Eurycoma longifolia Jack Against Drug-Resistant Plasmodium falciparum: An Integrated In Vitro and In Silico Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8108-2168","authenticated-orcid":false,"given":"Atthaphon","family":"Konyanee","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand"},{"name":"Center of Excellence in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat 80160, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8353-8679","authenticated-orcid":false,"given":"Habibah A.","family":"Wahab","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Pulau Pinang, Malaysia"},{"name":"Malaysian Institute of Pharmaceuticals and Nutraceuticals, National Institutes of Biotechnology Malaysia, Halaman Bukit Gambir, Gelugor 11700, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0635-1023","authenticated-orcid":false,"given":"Ezatul Ezleen","family":"Kamarulzaman","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Pulau Pinang, Malaysia"},{"name":"Faculty of Pharmacy, Universitas Airlangga, Kampus C UNAIR, Jl. 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