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This study aimed to identify secondary metabolites from actinomycete library extracts that are potent against the asexual stages of <jats:italic>Plasmodium<\/jats:italic><jats:italic>falciparum<\/jats:italic> (<jats:italic>P.<\/jats:italic><jats:italic>falciparum<\/jats:italic>).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Secondary metabolites from actinomycete library extracts were isolated from culture supernatants by ethyl acetate extraction. Comprehensive screening was performed to identify novel antimalarial compounds from the actinomycete library extracts (<jats:italic>n<\/jats:italic>\u2009=\u200928). The antimalarial activity was initially evaluated in vitro against chloroquine\/mefloquine-sensitive (3D7) and-resistant (Dd2) lines of <jats:italic>P.<\/jats:italic><jats:italic>falciparum<\/jats:italic>. The cytotoxicity was then evaluated in primary adult mouse brain (AMB) cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Out of the 28 actinomycete extracts, 17 showed parasite growth inhibition\u2009&gt;\u200950% at a concentration of 50\u00a0\u00b5g\/mL, nine were identified with an IC<jats:sub>50<\/jats:sub> value\u2009&lt;\u200910\u00a0\u00b5g\/mL, and seven suppressed the parasite significantly with an IC<jats:sub>50<\/jats:sub> value\u2009&lt;\u20095\u00a0\u00b5g\/mL. The extracts from <jats:italic>Streptomyces<\/jats:italic><jats:italic>aureus<\/jats:italic> strains HUT6003 (Extract ID number: 2),\u00a0<jats:italic>S.<\/jats:italic><jats:italic>antibioticus<\/jats:italic> HUT6035 (8), and <jats:italic>Streptomyces<\/jats:italic> sp. strains GK3 (26) and GK7 (27), were found to have the most potent antimalarial activity with IC<jats:sub>50<\/jats:sub> values of 0.39, 0.09, 0.97, and 0.36\u00a0\u00b5g\/mL (against 3D7), and 0.26, 0.22, 0.72, and 0.21\u00a0\u00b5g\/mL (against Dd2), respectively. Among them, <jats:italic>Streptomyces<\/jats:italic><jats:italic>antibioticus<\/jats:italic> strain HUT6035 (8) showed the highest antimalarial activity with an IC<jats:sub>50<\/jats:sub> value of 0.09\u00a0\u00b5g\/mL against 3D7 and 0.22\u00a0\u00b5g\/mL against Dd2, and a selective index (SI) of 188 and 73.7, respectively.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Secondary metabolites obtained from the actinomycete extracts showed promising antimalarial activity in vitro against 3D7 and Dd2 cell lines of <jats:italic>P.<\/jats:italic><jats:italic>falciparum<\/jats:italic> with minimal toxicity. Therefore, secondary metabolites obtained from actinomycete extracts represent an excellent starting point for the development of antimalarial drug leads.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s41182-024-00608-1","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T10:07:16Z","timestamp":1720519636000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Discovery of antimalarial drugs from secondary metabolites in actinomycetes culture library"],"prefix":"10.1186","volume":"52","author":[{"given":"Awet Alem","family":"Teklemichael","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiko","family":"Teshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asahi","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momoko","family":"Akimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gholam","family":"Khodakaramian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7442-5974","authenticated-orcid":false,"given":"Takashi","family":"Fujimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyuki","family":"Tokumasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5129-0042","authenticated-orcid":false,"given":"Kenji","family":"Arakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7722-4884","authenticated-orcid":false,"given":"Shusaku","family":"Mizukami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"608_CR1","unstructured":"<WHO WORLD MALARIA REPORT 2022.pdf>."},{"issue":"3","key":"608_CR2","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1056\/NEJMoa1710775","volume":"380","author":"MVG Lacerda","year":"2019","unstructured":"Lacerda MVG, Llanos-Cuentas A, Krudsood S, Lon C, Saunders DL, Mohammed R, et al. 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Int J Clin Exp Med. 2015;8(2):1904\u201311.","journal-title":"Int J Clin Exp Med"}],"container-title":["Tropical Medicine and Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41182-024-00608-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41182-024-00608-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41182-024-00608-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T10:07:23Z","timestamp":1720519643000},"score":1,"resource":{"primary":{"URL":"https:\/\/tropmedhealth.biomedcentral.com\/articles\/10.1186\/s41182-024-00608-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,9]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["608"],"URL":"https:\/\/doi.org\/10.1186\/s41182-024-00608-1","relation":{},"ISSN":["1349-4147"],"issn-type":[{"value":"1349-4147","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,9]]},"assertion":[{"value":"5 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Human RBCs and plasma were obtained and used after obtaining approval from the Institutional Ethical Review Board of the Institute of Tropical Medicine, Nagasaki University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflict of interest. Nagasaki University and Shionogi & Co., Ltd. launched the Shionogi Global Infectious Diseases Division at the Institute of Tropical Medicine, Nagasaki University. Although the authors of the division receive salaries from Nagasaki University, Shionogi & Co., Ltd. allocates the budget to Nagasaki University for their employment. However, Shionogi & Co., Ltd. did not play a role in this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"47"}}