{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:51:45Z","timestamp":1787313105881,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Drug therapy remains the principal management strategy for malaria but is increasingly challenged by the emergence of drug-resistant malaria parasites. The need for new antimalarial drugs is urgent, yet drug discovery and development are hindered by high costs, long durations, and safety concerns that prevent approval. The current study aimed to determine antiplasmodial activities of approved drugs in combination with artemether (ART) and lumefantrine (LU). Methods: Using the SYBR Green I assay test, this study investigated the efficacy of epirubicin (EPI) and pelitinib (PEL) combined with ART and LU at fixed drug\u2013drug ratios (4:1, 3:1, 1:1, 1:2, 1:3 and 1:4) and volume\/volume. These combinations, as well as single drug treatments, were tested against cultured strains of Plasmodium falciparum (W2, DD2, D6, 3D7 and F32-ART) and fresh and cultured clinical isolates. The fifty percent inhibition concentration (IC50) and a mean sum of fifty percent fractional inhibition concentration (FIC50) were determined. Results: Synergism was observed when EPI was combined with both ART and LU across all fixed ratios with a mean of mean FIC50 values of &lt;0.6. The combination of LU and EPI against the 3D7 strain demonstrated the highest efficacy with a synergism FIC50 value of 0.18. Most combinations of PEL with ART and LU showed antagonism (FIC50 &gt; 1) when tested against strains of P. falciparum and clinical isolates. Conclusions: This study underscores the utility of alternative drug discovery and development strategies to bypass cost, time, and safety barriers, thereby enriching the antimalarial drug pipeline and accelerating the transition from lab to market.<\/jats:p>","DOI":"10.3390\/ph18070956","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Antimalarial Drug Repurposing of Epirubicin and Pelitinib in Combination with Artemether and Lumefantrine"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7406-7492","authenticated-orcid":false,"given":"Douglas O.","family":"Ochora","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, School of Pure and Applied Sciences, Kisii University, Kisii P.O. Box 408-40200, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6454-1613","authenticated-orcid":false,"given":"Reagan M.","family":"Mogire","sequence":"additional","affiliation":[{"name":"Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20894, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard M.","family":"Murithi","sequence":"additional","affiliation":[{"name":"Medical Biotechnology and Immunotherapy Research Unit, Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town (UCT), Private Bag X3, Cape Town 7701, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farid","family":"Abdi","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute (KEMRI), Walter Reed Army Institute of Research-Africa, Kisumu P.O. Box 54-40100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick N.","family":"Ondari","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Pure and Applied Sciences, Kisii University, Kisii P.O. Box 408-40200, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rael J.","family":"Masai","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Pure and Applied Sciences, Kisii University, Kisii P.O. Box 408-40200, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1193-1989","authenticated-orcid":false,"given":"Edwin","family":"Mwakio","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute (KEMRI), Walter Reed Army Institute of Research-Africa, Kisumu P.O. Box 54-40100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Cheruyiot","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute (KEMRI), Walter Reed Army Institute of Research-Africa, Kisumu P.O. Box 54-40100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1123-3200","authenticated-orcid":false,"given":"Abiy","family":"Yenesew","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science and Technology, University of Nairobi, Nairobi P.O. Box 30197-00100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8584-2706","authenticated-orcid":false,"given":"Hoseah M.","family":"Akala","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute (KEMRI), Walter Reed Army Institute of Research-Africa, Kisumu P.O. 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