---
title: "Actinomycin Analogs From Streptomyces polyantibioticus S4D258 and Activity Against Triple‑Negative"
id: "pubmed-42814512"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42814512"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42814512/"
doi: "10.1002/cbdv.71791"
published_at: "2026-10-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Actinomycin Analogs From Streptomyces polyantibioticus S4D258 and Activity Against Triple‑Negative
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42814512
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42814512/)
- **DOI:** [10.1002/cbdv.71791](https://doi.org/10.1002%2Fcbdv.71791)
- **Published At:** 2026-10-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Fifteen new **actinomycin** analogs (designated actinomycins H1–H15) were isolated from the marine-derived Streptomyces polyantibioticus S4D258. - Structural elucidation used high-resolution electrospray ionization mass spectrometry (**HR-ESIMS**), nuclear magnetic resonance (**NMR**) spectroscopy, and Marfey's method. - Actinomycins H1–H5 contain L‑serine, D‑2‑aminobutyric acid, and L‑2‑methylaminobutyric acid residues; actinomycin H6 has a 5H‑oxazolo[4,5-b]phenoxazine chromophore. - Actinomycins H7–H15 are nine truncated analogs that contain only one pentapeptidolactone unit. - Two analogs, **actinomycin H1** and **actinomycin H9**, inhibited proliferation of triple‑negative breast cancer MDA‑MB‑231 cells with reported IC50 values of 28.00 nM and 4.34 µM, respectively. - Mechanistic assays showed these two compounds induced **S‑phase cell‑cycle arrest**, mitochondrial membrane potential depolarization, and **apoptosis**, and they also triggered **ferroptosis**. - Ferroptosis-associated findings included increased reactive oxygen species (ROS), enhanced lipid peroxidation, and elevated malondialdehyde (MDA) levels. - The study increases the known structural diversity of natural actinomycins and suggests re‑examining actinomycin analogs as anticancer leads for **triple‑negative breast cancer**. - Methods details, full spectra, and broader biological data are reported in the original article; additional experimental specifics were not reported in the PubMed abstract.
## Clinical Analysis & Structured Key Points
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R. China."), [Xiao-Min Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+XM&cauthor_id=42814512)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#full-view-affiliation-1 "Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts, School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China."), [Usama Ramadan Abdelmohsen](https://pubmed.ncbi.nlm.nih.gov/?term=Abdelmohsen+UR&cauthor_id=42814512)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#full-view-affiliation-2 "Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt."), [Li Shen](https://pubmed.ncbi.nlm.nih.gov/?term=Shen+L&cauthor_id=42814512)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#full-view-affiliation-1 "Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts, School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#full-view-affiliation-3 "Dongguan Key Laboratory For Marine Innovative Drugs and Bioproducts, Guangdong Medical University, Dongguan, P. R. China."), [Jun Wu](https://pubmed.ncbi.nlm.nih.gov/?term=Wu+J&cauthor_id=42814512)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#full-view-affiliation-1 "Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts, School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#full-view-affiliation-3 "Dongguan Key Laboratory For Marine Innovative Drugs and Bioproducts, Guangdong Medical University, Dongguan, P. R. China.") Affiliations Expand ### Affiliations * 1 Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts, School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China. * 2 Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt. * 3 Dongguan Key Laboratory For Marine Innovative Drugs and Bioproducts, Guangdong Medical University, Dongguan, P. R. China. * PMID: **42814512** * DOI: [ 10.1002/cbdv.71791 ](https://doi.org/10.1002/cbdv.71791) Item in Clipboard # Actinomycin Analogs From Streptomyces polyantibioticus S4D258: Structural Elucidation and Antiproliferative Activity Against Triple-Negative Breast Cancer He Pang et al. Chem Biodivers. 2026 Oct. Show details Display options Display options Format Abstract PubMed PMID Chem Biodivers Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Chem+Biodivers%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Chem+Biodivers%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) . 2026 Oct;23(10):e71791. doi: 10.1002/cbdv.71791. ### Authors [He Pang](https://pubmed.ncbi.nlm.nih.gov/?term=Pang+H&cauthor_id=42814512)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#short-view-affiliation-1 "Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts, School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China."), [Xiao-Min Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+XM&cauthor_id=42814512)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#short-view-affiliation-1 "Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts, School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China."), [Usama Ramadan Abdelmohsen](https://pubmed.ncbi.nlm.nih.gov/?term=Abdelmohsen+UR&cauthor_id=42814512)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#short-view-affiliation-2 "Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt."), [Li Shen](https://pubmed.ncbi.nlm.nih.gov/?term=Shen+L&cauthor_id=42814512)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#short-view-affiliation-1 "Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts, School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#short-view-affiliation-3 "Dongguan Key Laboratory For Marine Innovative Drugs and Bioproducts, Guangdong Medical University, Dongguan, P. R. China."), [Jun Wu](https://pubmed.ncbi.nlm.nih.gov/?term=Wu+J&cauthor_id=42814512)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#short-view-affiliation-1 "Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts, School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42814512/#short-view-affiliation-3 "Dongguan Key Laboratory For Marine Innovative Drugs and Bioproducts, Guangdong Medical University, Dongguan, P. R. China.") ### Affiliations * 1 Guangdong Provincial Engineering Technology Research Center for Innovative Drugs and Bioproducts, School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China. * 2 Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, Egypt. * 3 Dongguan Key Laboratory For Marine Innovative Drugs and Bioproducts, Guangdong Medical University, Dongguan, P. R. China. * PMID: **42814512** * DOI: [ 10.1002/cbdv.71791 ](https://doi.org/10.1002/cbdv.71791) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Fifteen new actinomycin analogs were obtained from the marine-derived Streptomyces polyantibioticus S4D258. Structural elucidation of these compounds was successfully achieved by comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HR-ESIMS), nuclear magnetic resonance spectroscopy (NMR), and Marfey's method. Notably, actinomycins H1-H5 (1-5) contain L-serine (L-Ser), D-2-aminobutyric acid (D-2-Aba), and L-2-methylaminobutyric acid (L-2-MeAba) residues, whereas actinomycin H6 (6) comprises a 5H-oxazolo[4,5-b]phenoxazine chromophore. Actinomycins H7-H15 (7-15) are nine truncated actinomycin analogs only containing one pentapeptidolactone unit. Actinomycins H1 (1) and H9 (9) exhibited inhibitory activities against the proliferation of triple-negative breast cancer MDA-MB-231 cells with IC50 values of 28.00 nM and 4.34 µM, respectively. Mechanistic investigation revealed that the above two actinomycin analogs not only induce S-phase 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-examination of actinomycin analogs as anticancer leads against triple-negative breast cancer. **Keywords:** actinomycins; ferroptosis; streptomyces polyantibioticus; triple‐negative breast cancer. © 2026 The Author(s). Chemistry & Biodiversity published by Wiley‐VHCA AG. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## References 1. 1. A. C. Garrido‐Castro, N. U. Lin, and K. Polyak, “Insights into Molecular Classifications of Triple‐Negative Breast Cancer: Improving Patient Selection for Treatment,” Cancer Discovery 9 (2019): 176–198, [https://doi.org/10.1158/2159‐8290.CD‐18‐1177](https://doi.org/10.1158/2159%E2%80%908290.CD%E2%80%9018%E2%80%901177). 2. 1. H. Kennecke, R. Yerushalmi, R. Woods, et al., “Metastatic Behavior of Breast Cancer Subtypes,” Journal of Clinical Oncology 28 (2010): 3271–3277, . 3. 1. J. Cortes, H. S. Rugo, D. W. Cescon, et al., “Pembrolizumab plus Chemotherapy in Advanced Triple‐Negative Breast Cancer,” New England Journal of Medicine 387 (2022): 217–226, . 4. 1. P. Zagami and L. A. Carey, “Triple Negative Breast Cancer: Pitfalls and Progress,” npj Breast Cancer 8 (2022): 95, [https://doi.org/10.1038/s41523‐022‐00468‐0](https://doi.org/10.1038/s41523%E2%80%90022%E2%80%9000468%E2%80%900). 5. 1. G. Bianchini, C. De Angelis, L. Licata, and L. Gianni, “Treatment Landscape of Triple‐Negative Breast Cancer—Expanded Options, Evolving Needs,” Nature Reviews Clinical Oncology 19 (2022): 91–113, [https://doi.org/10.1038/s41571‐021‐00565‐2](https://doi.org/10.1038/s41571%E2%80%90021%E2%80%9000565%E2%80%902). Show all 27 references ## MeSH terms * Antineoplastic Agents* / chemistry Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antineoplastic+Agents%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Antineoplastic+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Antineoplastic Agents* / isolation & purification Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antineoplastic+Agents%2Fisolation+and+purification%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Antineoplastic+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Antineoplastic Agents* / pharmacology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antineoplastic+Agents%2Fpharmacology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Antineoplastic+Agents) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Apoptosis / drug effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Apoptosis%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Apoptosis) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Cell Proliferation / drug effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Proliferation%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Proliferation) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Dactinomycin* / analogs & derivatives Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Dactinomycin%2Fanalogs+and+derivatives%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Dactinomycin) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Dactinomycin* / chemistry Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Dactinomycin%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Dactinomycin) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Dactinomycin* / isolation & purification Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Dactinomycin%2Fisolation+and+purification%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Dactinomycin) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Dactinomycin* / pharmacology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Dactinomycin%2Fpharmacology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Dactinomycin) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Dose-Response Relationship, Drug Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Dose-Response+Relationship%2C+Drug%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Dose-Response+Relationship%2C+Drug) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Drug Screening Assays, Antitumor Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Drug+Screening+Assays%2C+Antitumor%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Drug+Screening+Assays%2C+Antitumor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * MDA-MB-231 Cells Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22MDA-MB-231+Cells%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=MDA-MB-231+Cells) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Membrane Potential, Mitochondrial / drug effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Membrane+Potential%2C+Mitochondrial%2Fdrug+effects%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Membrane+Potential%2C+Mitochondrial) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Molecular Structure Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Molecular+Structure%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Molecular+Structure) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42814512/) * Reactive Oxygen Speci
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