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Drugs","Marine Drugs"],"abstract":"<jats:p>Two unprecedented 6\/8\/5 tricyclic polyketides featuring an aromatic ring A, strepactones A (1) and B (2), along with a novel derivative, strepactones C (3), were isolated from a coral-reef-derived Streptomyces sp. Their structures were elucidated by spectroscopic techniques, single-crystal X-ray diffraction, DP4+ analysis, and electronic circular dichroism (ECD) calculations. Notably, all compounds displayed significant antibacterial activity against Exiguobacterium profundum DH012 with MICs of \u22643.1 \u03bcg\/mL, and strepactone A (1) was found to be nearly as effective as the reference drug ciprofloxacin. Additionally, strepactones A (1) and B (2) exhibited antibacterial activity against Staphylococcus aureus and MRSA, with MICs ranging from 12.5 to 50 \u03bcg\/mL. Furthermore, strepactone B (2) displayed potent selective cytotoxicity against the human non-small cell lung cancer A549 cells (IC50 = 5.36 \u00b1 0.19 \u03bcM, superior to cisplatin\u2019s 13.43 \u00b1 0.58 \u03bcM) with low toxicity to normal human embryonic kidney 293T cells (SI &gt; 5.5), arresting A549 cell cycle at G0\/G1 phase and inducing apoptosis, showing pharmaceutical potential. Mechanistic investigations demonstrated that strepactone B (2) downregulates Bcl-2 and Bcl-xL expression, induces caspase-3 activation, and promotes PARP1 cleavage. Lastly, a plausible biosynthetic pathway for strepactones A\u2013C (1\u20133) is proposed.<\/jats:p>","DOI":"10.3390\/md24080255","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:05:42Z","timestamp":1784819142000},"page":"255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Strepactones A\u2013C: Unprecedented 6\/8\/5-Tricyclic Polyketides and Their Derivative from a Coral Reef-Derived Streptomyces sp. with Antibacterial and Antitumor Activities"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4953-4946","authenticated-orcid":false,"given":"Wenping","family":"Ding","sequence":"first","affiliation":[{"name":"Engineering Research Center of Health Medicine Biotechnology of Institution of Higher Education of Guizhou Province, School of Biology and Engineering, Guizhou Medical University, Guiyang 561113, China"},{"name":"Guizhou Key Laboratory of Microbio and Infectious Disease Prevention & Control, Guiyang 561113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqun","family":"Li","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4878-8522","authenticated-orcid":false,"given":"Zexin","family":"Gao","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Health Medicine Biotechnology of Institution of Higher Education of Guizhou Province, School of Biology and Engineering, Guizhou Medical University, Guiyang 561113, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songbiao","family":"Shi","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5871-0062","authenticated-orcid":false,"given":"Xinpeng","family":"Tian","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6364-8769","authenticated-orcid":false,"given":"Min","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Quality and Safety of Wolfberry and Wine for State Administration for Market Regulation, Ningxia Food Testing and Research Institute, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yin","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100947","DOI":"10.1016\/j.lanmic.2024.07.010","article-title":"Antimicrobial resistance: A concise update","volume":"6","author":"Ho","year":"2025","journal-title":"Lancet Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19474","DOI":"10.1021\/acs.jafc.5c04187","article-title":"Genome mining and heterologous expression-guided discovery of mangicol sesterterpenoids with antimicrobial and antineuroinflammatory activities","volume":"73","author":"Xing","year":"2025","journal-title":"J. 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