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Pilot screening showed significant antimalarial activity in\n                    <jats:italic>Streptomyces antibioticus<\/jats:italic>\n                    HUT6035 (synonym of strain NBRC3117). We here isolated antimalarial compounds through large-scale fermentation and subsequent purification using chromatographies. Strain HUT6035 accumulated actinomycins X\n                    <jats:sub>2<\/jats:sub>\n                    and X\n                    <jats:sub>0\u00df<\/jats:sub>\n                    , which were 4-oxo and 4-hydroxy proline derivatives of actinomycin D, respectively. The former showed an antimalaria activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.241\u2009nM) and a cytotoxicity (CC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20096.71\u2009nM), while the latter showed IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20097.69\u2009nM and CC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u2009818\u2009nM. Compared with commercially available actinomycin D (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.469\u2009nM and CC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20096.71\u2009nM), both actinomycins X\n                    <jats:sub>2<\/jats:sub>\n                    and X\n                    <jats:sub>0\u00df<\/jats:sub>\n                    have significant selectivity index (SI) values (CC\n                    <jats:sub>50<\/jats:sub>\n                    \/IC\n                    <jats:sub>50<\/jats:sub>\n                    ) with 27.9 and 106. These SI values were two- and seven-fold preferential against that of actinomycin D (SI\u2009=\u200914.3). Thus, actinomycin derivatives are potential antimalarial agents.\n                  <\/jats:p>","DOI":"10.1038\/s41429-026-00924-0","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:01:48Z","timestamp":1778155308000},"page":"461-468","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of actinomycin derivatives with improved selectivity against malaria parasites from a Streptomyces culture library"],"prefix":"10.1038","volume":"79","author":[{"given":"Aiko","family":"Teshima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awet Alem","family":"Teklemichael","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":"Rukman","family":"Muslimin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Ogaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alimuddin","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shusaku","family":"Mizukami","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"}]}],"member":"297","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"924_CR1","doi-asserted-by":"publisher","first-page":"6420","DOI":"10.1016\/j.tet.2011.03.117","volume":"67","author":"S \u014cmura","year":"2011","unstructured":"\u014cmura S. 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Nagasaki University and Shionogi & Co., Ltd. launched the Shionogi Global Infectious Diseases Division at the Institute of Tropical Medicine, Nagasaki University. M.T. and S.M. receive salaries from the budget to Nagasaki University for their employment. However, Shionogi & Co., Ltd. did not play a role in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}