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Structural elucidation of these compounds was successfully achieved by comprehensive analysis of high\u2010resolution electrospray ionization mass spectrometry (HR\u2010ESIMS), nuclear magnetic resonance spectroscopy (NMR), and Marfey's method. Notably, actinomycins H\n                    <jats:sub>1<\/jats:sub>\n                    \u2013H\n                    <jats:sub>5<\/jats:sub>\n                    (\n                    <jats:bold>1<\/jats:bold>\n                    \u2013\n                    <jats:bold>5<\/jats:bold>\n                    ) contain\n                    <jats:italic>L<\/jats:italic>\n                    \u2010serine (\n                    <jats:italic>L<\/jats:italic>\n                    \u2010Ser),\n                    <jats:italic>D<\/jats:italic>\n                    \u20102\u2010aminobutyric acid (\n                    <jats:italic>D<\/jats:italic>\n                    \u20102\u2010Aba), and\n                    <jats:italic>L<\/jats:italic>\n                    \u20102\u2010methylaminobutyric acid (\n                    <jats:italic>L<\/jats:italic>\n                    \u20102\u2010MeAba) residues, whereas actinomycin H\n                    <jats:sub>6<\/jats:sub>\n                    (\n                    <jats:bold>6<\/jats:bold>\n                    ) comprises a 5\n                    <jats:italic>H<\/jats:italic>\n                    \u2010oxazolo[4,5\u2010\n                    <jats:italic>b<\/jats:italic>\n                    ]phenoxazine chromophore. Actinomycins H\n                    <jats:sub>7<\/jats:sub>\n                    \u2013H\n                    <jats:sub>15<\/jats:sub>\n                    (\n                    <jats:bold>7<\/jats:bold>\n                    \u2013\n                    <jats:bold>15<\/jats:bold>\n                    ) are nine truncated actinomycin analogs only containing one pentapeptidolactone unit. Actinomycins H\n                    <jats:sub>1<\/jats:sub>\n                    (\n                    <jats:bold>1<\/jats:bold>\n                    ) and H\n                    <jats:sub>9<\/jats:sub>\n                    (\n                    <jats:bold>9<\/jats:bold>\n                    ) exhibited inhibitory activities against the proliferation of triple\u2010negative breast cancer MDA\u2010MB\u2010231 cells with IC50 values of 28.00\u00a0nM and 4.34\u00a0\u00b5M, respectively. Mechanistic investigation revealed that the above two actinomycin analogs not only induce S\u2010phase arrest, mitochondrial membrane potential depolarization, and apoptosis, but also trigger ferroptosis, as revealed by an increase in the level of reactive oxygen species, lipid peroxidation, and malondialdehyde. Collectively, our findings enriched the structural diversity of natural actinomycins and inspired the re\u2010examination of actinomycin analogs as anticancer leads against triple\u2010negative breast cancer.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.71791","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:06:34Z","timestamp":1790784394000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Actinomycin Analogs From\n                    <i>Streptomyces polyantibioticus<\/i>\n                    S4D258: Structural Elucidation and Antiproliferative Activity Against Triple\u2010Negative Breast Cancer"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4736-1191","authenticated-orcid":false,"given":"He","family":"Pang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts School of Pharmacy Guangdong Medical University  Dongguan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Min","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts School of Pharmacy Guangdong Medical University  Dongguan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-6922","authenticated-orcid":false,"given":"Usama Ramadan","family":"Abdelmohsen","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy Faculty of Pharmacy Minia University  Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5770-1607","authenticated-orcid":false,"given":"Li","family":"Shen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts School of Pharmacy Guangdong Medical University  Dongguan P. R. China"},{"name":"Dongguan Key Laboratory For Marine Innovative Drugs and Bioproducts Guangdong Medical University  Dongguan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0807-5229","authenticated-orcid":false,"given":"Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts School of Pharmacy Guangdong Medical University  Dongguan P. R. China"},{"name":"Dongguan Key Laboratory For Marine Innovative Drugs and Bioproducts Guangdong Medical University  Dongguan P. R. 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