{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T08:56:51Z","timestamp":1769417811494,"version":"3.49.0"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2024YFC2815900"],"award-info":[{"award-number":["2024YFC2815900"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["U23A20107"],"award-info":[{"award-number":["U23A20107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22037006"],"award-info":[{"award-number":["22037006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2023B1515120053"],"award-info":[{"award-number":["2023B1515120053"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shenzhen Science and Technology Program","award":["20231128110730001"],"award-info":[{"award-number":["20231128110730001"]}]},{"name":"Rising Star Foundation of the South China Sea Institute of Oceanology","award":["NHXX2019SW0101"],"award-info":[{"award-number":["NHXX2019SW0101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Three new pyrrole alkaloids, streptopyrroles D\u2013F (1\u20133), along with four known analogs (4\u20137) were isolated from Sea Anemone-Associated Streptomyces sp. S1502 via an OSMAC (One Strain Many Compounds)-based strategy. Their structures were elucidated through comprehensive spectroscopic analyses, including HRESIMS and 1D\/2D NMR experiments (COSY, HSQC, and HMBC), and further confirmed by X-ray crystallography. Biological evaluation identified streptopyrrole (4) as an anti-MRSA (methicillin-resistant Staphylococcus aureus) agent, while 4 and 6 displayed broad-spectrum cytotoxicity and good selectivity against a panel of human cancer cell lines. Notably, 4 and 6 showed particularly potent activity against the lung cancer cell lines H1299, SW1573, and A549, with IC50 values ranging from 5.43 to 16.24 \u03bcM. Further mechanistic investigation revealed that both compounds suppress the proliferation of lung cancer cells by inducing cell cycle arrest at the G0\/G1 phase and impair metastatic potential by inhibiting migration and invasion. These findings not only expand the structural diversity of marine-derived pyrrole alkaloids but also reveal the anticancer mechanisms of 4 and 6, highlighting their promise as active candidates for further antitumor drug development, particularly in lung cancer.<\/jats:p>","DOI":"10.3390\/md24010051","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T13:59:54Z","timestamp":1769003994000},"page":"51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isolation, Structural Elucidation, and Biological Evaluation of Pyrrole-Based Alkaloids from Sea Anemone-Associated Streptomyces sp. S1502"],"prefix":"10.3390","volume":"24","author":[{"given":"Xin","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China"},{"name":"College of Oceanology, University of Chinese Academy of Sciences, Qingdao 266400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihong","family":"Yang","sequence":"additional","affiliation":[{"name":"People\u2019s Hospital of Longhua, Shenzhen 518109, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-8027","authenticated-orcid":false,"given":"Jianhua","family":"Ju","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China"},{"name":"College of Oceanology, University of Chinese Academy of Sciences, Qingdao 266400, China"},{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Key Laboratory of Chemical Biology (Ministry of Education), Shandong Basic Science Research Center (Pharmacy), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-7291","authenticated-orcid":false,"given":"Junying","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China"},{"name":"College of Oceanology, University of Chinese Academy of Sciences, Qingdao 266400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1039\/D3NP00061C","article-title":"Marine natural products","volume":"41","author":"Carroll","year":"2024","journal-title":"Nat. Prod. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"538","DOI":"10.2174\/1573406419666221202144044","article-title":"Marine-derived natural products as anticancer agents","volume":"19","author":"Saini","year":"2023","journal-title":"Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Liu, Z., Sun, W., Hu, Z., Wang, W., and Zhang, H. (2024). Marine streptomyces-derived novel alkaloids discovered in the past decade. Mar. Drugs, 22.","DOI":"10.3390\/md22010051"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Alam, K., Mazumder, A., Sikdar, S., Zhao, Y.M., Hao, J., Song, C., Wang, Y., Sarkar, R., Islam, S., and Zhang, Y. (2022). Streptomyces: The biofactory of secondary metabolites. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.968053"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/d41586-024-02661-6","article-title":"Bioprospecting marine microbial genomes to improve biotechnology","volume":"633","author":"Eren","year":"2024","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41586-024-07891-2","article-title":"Global marine microbial diversity and its potential in bioprospecting","volume":"633","author":"Chen","year":"2024","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1038\/s41467-021-24133-5","article-title":"Mining and unearthing hidden biosynthetic potential","volume":"12","author":"Scherlach","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, Y., Gong, N., Zhou, L., Yang, Z., Zhang, H., Gu, Y., Ma, J., and Ju, J. (2023). OSMAC-based discovery and biosynthetic gene clusters analysis of secondary metabolites from marine-derived Streptomyces globisporus SCSIO LCY30. Mar. Drugs, 22.","DOI":"10.3390\/md22010021"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7920","DOI":"10.1021\/acs.orglett.5c02239","article-title":"Discovery, structural revision, heterologous production, and biosynthesis of mintaimycins from marine-derived Micromonospora sp. SCSIO 80128","volume":"27","author":"Li","year":"2025","journal-title":"Org. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11284","DOI":"10.1021\/acs.orglett.5c03588","article-title":"Chlorobactine a, a dimeric dichlorated metabolite from marine-derived Streptomyces thermolineatus NAK03196","volume":"27","author":"Zhang","year":"2025","journal-title":"Org. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1021\/acs.jnatprod.1c01115","article-title":"Cytotoxic bromine- and iodine-containing cytochalasins produced by the mangrove endophytic fungus Phomopsis sp. QYM-13 using the OSMAC approach","volume":"85","author":"Chen","year":"2022","journal-title":"J. Nat. Prod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/s41579-020-0379-y","article-title":"Ecology and genomics of actinobacteria: New concepts for natural product discovery","volume":"18","author":"Terlouw","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18228","DOI":"10.1039\/c3ra42661k","article-title":"Biosynthesis of natural products by microbial iterative hybrid PKS-NRPS","volume":"3","author":"Fisch","year":"2013","journal-title":"RSC Adv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1021\/jacsau.4c00279","article-title":"An enzymatic oxidation cascade converts delta-thiolactone anthracene to anthraquinone in the biosynthesis of anthraquinone-fused enediynes","volume":"4","author":"Ma","year":"2024","journal-title":"JACS Au"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1021\/acs.orglett.7b01083","article-title":"Nam7 hydroxylase is responsible for the formation of the naphthalenic ring in the biosynthesis of neoansamycins","volume":"19","author":"Zhang","year":"2017","journal-title":"Org. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1021\/ol063102o","article-title":"Biosynthetic convergence of salinosporamides A and B in the marine actinomycete Salinispora tropica","volume":"9","author":"Beer","year":"2007","journal-title":"Org. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"116470","DOI":"10.1016\/j.ejmech.2024.116470","article-title":"Pyrrole-containing hybrids as potential anticancer agents: An insight into current developments and structure-activity relationships","volume":"273","author":"Long","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1021\/acscentsci.4c01167","article-title":"An optimized marinopyrrole A derivative targets 6-phosphoglucosamine synthetase to inhibit methicillin-resistant Staphylococcus aureus","volume":"10","author":"Guo","year":"2024","journal-title":"ACS Cent. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/1751-7915.13807","article-title":"Armeniaspirol A: A novel anti-Helicobacter pylori agent","volume":"15","author":"Jia","year":"2022","journal-title":"Microb. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.3891\/acta.chem.scand.52-1040","article-title":"Streptopyrrole: An antimicrobial metabolite from Streptomyces armeniacus","volume":"52","author":"Breinholt","year":"1998","journal-title":"Acta Chem. Scand."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7164\/antibiotics.53.1","article-title":"Novel streptopyrroles from Streptomyces rimosus with bacterial protein histidine kinase inhibitory and antimicrobial activities","volume":"53","author":"Trew","year":"2000","journal-title":"J. Antibiot."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Heo, C.S., Kang, J.S., Kwon, J.H., Anh, C.V., and Shin, H.J. (2023). Pyrrole-containing alkaloids from a marine-derived actinobacterium Streptomyces zhaozhouensis and their antimicrobial and cytotoxic activities. Mar. Drugs, 21.","DOI":"10.3390\/md21030167"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhou, L., Pan, X., Liao, Z., Qi, N., Sun, M., Zhang, H., Ju, J., and Ma, J. (2024). Metabolic blockade-based genome mining of sea anemone-associated Streptomyces sp. S1502 identifies atypical angucyclines WS-5995 A-E: Isolation, identification, biosynthetic investigation, and bioactivities. Mar. Drugs, 22.","DOI":"10.3390\/md22050195"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1021\/acs.jnatprod.5c00988","article-title":"Synergizing a metabolic blockade and non-reducing polyketide synthase substrate flexibility expand depsidone diversity in a marine-derived Aspergillus species","volume":"88","author":"Liu","year":"2025","journal-title":"J. Nat. Prod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1186\/s12964-024-01698-4","article-title":"BI-2865, a pan-KRAS inhibitor, reverses the P-glycoprotein induced multidrug resistance in vitro and in vivo","volume":"22","author":"Yang","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"175628","DOI":"10.1016\/j.ejphar.2023.175628","article-title":"Novel PORCN inhibitor WHN-88 targets Wnt\/\u03b2-catenin pathway and prevents the growth of Wnt-driven cancers","volume":"945","author":"Yang","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1074\/jbc.RA119.011396","article-title":"Parthenolide inhibits ubiquitin-specific peptidase 7 (USP7), Wnt signaling, and colorectal cancer cell growth","volume":"295","author":"Li","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/s41418-024-01342-1","article-title":"Ubiquitin-specific protease 1 facilitates hepatocellular carcinoma progression by modulating mitochondrial fission and metabolic reprogramming via cyclin-dependent kinase 5 stabilization","volume":"31","author":"Bian","year":"2024","journal-title":"Cell Death Differ."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/1\/51\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T18:36:39Z","timestamp":1769193399000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/1\/51"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["md24010051"],"URL":"https:\/\/doi.org\/10.3390\/md24010051","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]}}}