{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T06:02:21Z","timestamp":1772344941635,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003566","name":"Ministry of Oceans and Fisheries, Republic of Korea","doi-asserted-by":"publisher","award":["PG54141"],"award-info":[{"award-number":["PG54141"]}],"id":[{"id":"10.13039\/501100003566","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003566","name":"Ministry of Oceans and Fisheries, Republic of Korea","doi-asserted-by":"publisher","award":["PEA0311"],"award-info":[{"award-number":["PEA0311"]}],"id":[{"id":"10.13039\/501100003566","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003566","name":"Ministry of Oceans and Fisheries, Republic of Korea","doi-asserted-by":"publisher","award":["PEA0314"],"award-info":[{"award-number":["PEA0314"]}],"id":[{"id":"10.13039\/501100003566","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korea Institute of Ocean Science and Technology","award":["PG54141"],"award-info":[{"award-number":["PG54141"]}]},{"name":"Korea Institute of Ocean Science and Technology","award":["PEA0311"],"award-info":[{"award-number":["PEA0311"]}]},{"name":"Korea Institute of Ocean Science and Technology","award":["PEA0314"],"award-info":[{"award-number":["PEA0314"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Four new kaurane-type diterpenoids, geliboluols A\u2013D (1\u20134), along with one known analog (5), were isolated from the culture broth of the marine-derived rare actinomycete Actinomadura geliboluensis. The structures of compounds 1\u20134 were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR), the MPA method, and by comparing their optical rotation values with those in the literature. The new compounds were evaluated for their cytotoxicity against seven blood cancer cell lines by a CellTiter-Glo (CTG) assay and six solid cancer cell lines by a sulforhodamine B (SRB) assay. Among the new compounds, compound 4 exhibited moderate cytotoxic activity against some blood cancer cell lines, with GI50 values ranging from 2.59 to 19.64 \u00b5M, and against solid cancer cell lines with GI50 values ranging from 4.34 to 7.23 \u00b5M.<\/jats:p>","DOI":"10.3390\/md23020078","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T11:08:51Z","timestamp":1739358531000},"page":"78","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Geliboluols A\u2013D: Kaurane-Type Diterpenoids from the Marine-Derived Rare Actinomycete Actinomadura geliboluensis"],"prefix":"10.3390","volume":"23","author":[{"given":"Chang-Su","family":"Heo","sequence":"first","affiliation":[{"name":"Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, 385 Haeyang-ro, Busan 49111, Republic of Korea"},{"name":"Department of Marine Technology and Convergence Engineering, University of Science and Technology (UST), 217 Gajungro, Daejeon 34113, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Soon","family":"Kang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 28116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong-Wook","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 28116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Ah","family":"Lee","sequence":"additional","affiliation":[{"name":"Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, 385 Haeyang-ro, Busan 49111, Republic of Korea"},{"name":"Department of Chemistry, Pukyong National University, 45 Yongso-ro, Busan 48513, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0435-5688","authenticated-orcid":false,"given":"Hwa-Sun","family":"Lee","sequence":"additional","affiliation":[{"name":"Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, 385 Haeyang-ro, Busan 49111, Republic of Korea"},{"name":"Department of Chemistry, Pukyong National University, 45 Yongso-ro, Busan 48513, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Dokdo Research Center, Korea Institute of Ocean Science and Technology, Uljin 36315, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5952-5325","authenticated-orcid":false,"given":"Hee Jae","family":"Shin","sequence":"additional","affiliation":[{"name":"Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, 385 Haeyang-ro, Busan 49111, Republic of Korea"},{"name":"Department of Marine Technology and Convergence Engineering, University of Science and Technology (UST), 217 Gajungro, Daejeon 34113, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.lfs.2006.05.015","article-title":"Kaurane and pimarane-type diterpenes from the Viguiera species inhibit vascular smooth muscle contractility","volume":"79","author":"Ambrosio","year":"2006","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3390\/12030455","article-title":"Occurrence, biological activities and synthesis of kaurane diterpenes and their glycosides","volume":"12","author":"Batista","year":"2007","journal-title":"Molecules"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1039\/D1NP00028D","article-title":"Recent advances in the synthesis of ent-kaurane diterpenoids","volume":"39","author":"Zhao","year":"2022","journal-title":"Nat. Prod. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ibrahim, T.S., Khongorzul, P., Muyaba, M., and Alolga, R.N. (2023). Ent-kaurane diterpenoids from the Annonaceae family: A review of research progress and call for further research. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1227574"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.plaphy.2022.12.013","article-title":"Diterpenes of Coffea seeds show antifungal and anti-insect activities and are transferred from the endosperm to the seedling after germination","volume":"194","author":"Antoine","year":"2023","journal-title":"Plant Physiol. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/tpj.12436","article-title":"Biosynthesis, elicitation and roles of monocot terpenoid phytoalexins","volume":"79","author":"Schmelz","year":"2014","journal-title":"Plant J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Herrera-Acevedo, C., Flores-Gaspar, A., Scotti, L., Mendon\u00e7a-Junior, F.J.B., Scotti, M.T., and Coy-Barrera, E. (2021). Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I. Molecules, 26.","DOI":"10.3390\/molecules26113076"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1021\/np8003062","article-title":"ent-Kaurane Diterpenoids from the Liverwort Jungermannia atrobrunnea","volume":"71","author":"Qu","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhou, Z.-S., Wang, Z.-J., Tian, B., Zhu, Y.-Y., Wei, M.-Z., Zhao, Y.-L., and Luo, X.-D. (2024). Three New Ent-Kaurane Diterpenes with Antibacterial Activity from Sigesbeckia orientalis. Molecules, 29.","DOI":"10.3390\/molecules29194631"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hai, Q.X., Hu, K., Chen, S.P., Fu, Y.Y., Li, X.N., Sun, H.D., He, H.P., and Puno, P.T. (2024). Silvaticusins A-D: Ent-kaurane diterpenoids and a cyclobutane-containing ent-kaurane dimer from Isodon silvaticus. Nat. Prod. Bioprospect., 14.","DOI":"10.1007\/s13659-024-00465-9"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1021\/acs.jnatprod.9b01281","article-title":"Anti-Inflammatory ent-Kaurane Diterpenoids from Isodon serra","volume":"83","author":"Xing","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1021\/np960416j","article-title":"Identification of ent-16\u03b2,17-Dihydroxykauran-19-oic Acid as an Anti-HIV Principle and Isolation of the New Diterpenoids Annosquamosins A and B from Annona squamosa","volume":"59","author":"Wu","year":"1996","journal-title":"J. Nat. Prod."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Schniete, J.K., and Fern\u00e1ndez-Mart\u00ednez, L.T. (2024). Natural product discovery in soil actinomycetes: Unlocking their potential within an ecological context. Curr. Opin. Microbio., 79.","DOI":"10.1016\/j.mib.2024.102487"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Law, J.W.-F., Law, L.N.-S., Letchumanan, V., Tan, L.T.-H., Wong, S.H., Chan, K.-G., Ab Mutalib, N.-S., and Lee, L.-H. (2020). Anticancer Drug Discovery from Microbial Sources: The Unique Mangrove Streptomycetes. Molecules, 25.","DOI":"10.3390\/molecules25225365"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1039\/C4NP00167B","article-title":"The marine actinomycete genus Salinispora: A model organism for secondary metabolite discovery","volume":"32","author":"Jensen","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1039\/D3NP00047H","article-title":"Chemistry and biology of specialized metabolites produced by Actinomadura","volume":"41","author":"Dashti","year":"2024","journal-title":"Nat. Prod. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1021\/acs.jnatprod.6b00268","article-title":"Actinomadurol, an Antibacterial Norditerpenoid from a Rare Actinomycete, Actinomadura sp. KC 191","volume":"79","author":"Shin","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.chembiol.2020.06.011","article-title":"Pharmacological Targeting of Vacuolar H+-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer","volume":"27","author":"Wang","year":"2020","journal-title":"Cell Chem. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"75","DOI":"10.7150\/jgen.19673","article-title":"Complete Genome Sequence of Actinomadura parvosata subsp. kistnae, a rich source of novel natural product (bio-) chemistry","volume":"5","author":"Kusserow","year":"2017","journal-title":"J. Genom."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Saricaoglu, S., Saygin, H., Topkara, A.R., Gencbay, T., Guven, K., Cetin, D., Sahin, N., and Isik, K. (2021). Actinomadura soli sp. nov., isolated from the top soil layer on basaltic material in Turkey. Int. J. Syst. Evol. Microbiol., 71.","DOI":"10.1099\/ijsem.0.005062"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10482-020-01511-5","article-title":"Genomic insight into a novel actinobacterium, Actinomadura rubrisoli sp. nov., reveals high potential for bioactive metabolites","volume":"114","author":"Ay","year":"2021","journal-title":"Antonie Leeuwenhoek"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Parra, J., Beaton, A., Seipke, R.F., Wilkinson, B., Hutchings, M.I., and Duncan, K.R. (2023). Antibiotics from rare actinomycetes, beyond the genus Streptomyces. Curr. Opin. Microbiol., 76.","DOI":"10.1016\/j.mib.2023.102385"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1099\/ijs.0.036145-0","article-title":"Actinomadura geliboluensis sp. nov., isolated from soil","volume":"62","author":"Sazak","year":"2012","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.3762\/bjoc.17.141","article-title":"Nomimicins B-D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura","volume":"17","author":"Zhang","year":"2021","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1021\/np070383f","article-title":"Crotonkinins A and B and Related Diterpenoids from Croton tonkinensis as Anti-inflammatory and Antitumor Agents","volume":"70","author":"Kuo","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1016\/S0031-9422(00)82471-1","article-title":"Foliage sesquiterpenes and diterpenes of Podocarpus spicatus","volume":"26","author":"Lorimer","year":"1987","journal-title":"Phytochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1021\/acs.jnatprod.7b01017","article-title":"ent-Kaurane Diterpenoids with Neuroprotective Properties from Corn Silk (Zea mays)","volume":"81","author":"Qi","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1021\/acs.jafc.6b05376","article-title":"Novel ent-Kaurane Diterpenoid from Rubus corchorifolius L. f. Inhibits Human Colon Cancer Cell Growth via Inducing Cell Cycle Arrest and Apoptosis","volume":"65","author":"Chen","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.phytol.2015.01.004","article-title":"Two new ent-kaurane diterpenoids from Wedelia trilobata (L.) Hitchc","volume":"11","author":"Ren","year":"2015","journal-title":"Phytochem. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1021\/np4010135","article-title":"Cytotoxic ent-Kaurane Diterpenoids from Isodon wikstroemioides","volume":"77","author":"Wu","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6629","DOI":"10.1016\/j.tet.2015.04.116","article-title":"New avenues for the synthesis of ent-kaurene diterpenoids","volume":"71","author":"Riehl","year":"2015","journal-title":"Tetrahedron"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1248\/cpb.51.790","article-title":"Ent-kaurane diterpenoids from Isodon rubescens var","volume":"51","author":"Han","year":"2003","journal-title":"lushanensis. Chem. Pharm. Bull."},{"key":"ref_33","unstructured":"CLSI (2018). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, Clinical and Laboratory Standards Institute. [11th ed.]. CLSI Standard M07."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Choi, B.-K., Trinh, P.T.H., Lee, H.-S., Choi, B.-W., Kang, J.S., Ngoc, N.T.D., Van, T.T.T., and Shin, H.J. (2019). New Ophiobolin Derivatives from the Marine Fungus Aspergillus flocculosus and Their Cytotoxicities against Cancer Cells. Mar. Drugs, 17.","DOI":"10.3390\/md17060346"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lee, E., Cho, H., Lee, D.K., Ha, J., Choi, B.J., Jeong, J.H., Ryu, J.-H., Kang, J.S., and Jeon, R. (2020). Discovery of 5-Phenoxy-2-aminopyridine Derivatives as Potent and Selective Irreversible Inhibitors of Bruton\u2019s Tyrosine Kinase. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218006"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/23\/2\/78\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:30:44Z","timestamp":1760027444000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/23\/2\/78"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,10]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["md23020078"],"URL":"https:\/\/doi.org\/10.3390\/md23020078","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,10]]}}}