{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:11:36Z","timestamp":1770898296206,"version":"3.50.1"},"reference-count":80,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health Grant","award":["5P20GM103427"],"award-info":[{"award-number":["5P20GM103427"]}]},{"name":"The University of Nebraska GRACA, FUSE, and NU Collaboration Initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Marine-derived secondary metabolites have emerged as a rich potential source of anticancer agents, with marinopyrroles and pyrrolomycins representing structurally distinct halogenated pyrroles of interest. Initially characterized for their potent antibacterial properties, these compounds were later shown to exert cytotoxic activity across diverse hematologic and solid malignancies, frequently correlating with Mcl-1 dependence. Marinopyrrole A, a marine-derived natural product, exemplified this potential by inducing proteasomal degradation of Mcl-1, thereby sensitizing resistant cancer cells to Bcl-2 inhibitors and TRAIL-based therapies. In parallel, pyrrolomycins, particularly pyrrolomycin C and members of the F-series, demonstrated potent activity with submicromolar IC50 concentrations across multiple cancer cell lines, and also perturbed cytoskeletal and membrane integrity. Together, these halogenated pyrroles illustrate multifaceted cancer cell cytotoxicity profiles but face translational barriers, including mechanistic ambiguity, poor solubility, and off-target toxicities. To address these limitations, extensive medicinal chemistry efforts have yielded synthetic derivatives with improved potency, selectivity, and drug-like properties, with notable examples such as MP1 and KS18 showing enhanced efficacy in MYC-driven neuroblastoma, medulloblastoma, and drug-resistant multiple myeloma.<\/jats:p>","DOI":"10.3390\/md23100403","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T07:33:50Z","timestamp":1760686430000},"page":"403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cancer Cell Cytotoxicity of Marinopyrroles, Pyrrolomycins, and Their Derivatives"],"prefix":"10.3390","volume":"23","author":[{"given":"Jeffrey M.","family":"Zimmerly","sequence":"first","affiliation":[{"name":"Department of Biology, University of Nebraska at Omaha, Omaha, NE 68182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas A.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Nebraska at Omaha, Omaha, NE 68182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8193-9732","authenticated-orcid":false,"given":"Clare F.","family":"Euteneuer","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Nebraska at Omaha, Omaha, NE 68182, USA"},{"name":"College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3230-4378","authenticated-orcid":false,"given":"Brianna N.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Nebraska at Omaha, Omaha, NE 68182, USA"},{"name":"Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84604, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Beth","family":"Griffis-Anchala","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Nebraska at Omaha, Omaha, NE 68182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2558-7992","authenticated-orcid":false,"given":"Angelique","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Nebraska at Omaha, Omaha, NE 68182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0526-3841","authenticated-orcid":false,"given":"Paul H.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Nebraska at Omaha, Omaha, NE 68182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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