{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T18:55:12Z","timestamp":1771872912819,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Halosmysin A, a new 14-membered macrodiolide with an unprecedented skeleton, was isolated from the fungus Halosphaeriaceae sp. OUPS-135D-4, which, in turn, was obtained from the marine algae Sargassum thunbergii. The chemical structure of the macrodiolide was elucidated using 1D and 2D NMR, as well as high resolution fast atom bombardment mass (HRFABMS) spectral analysis. The absolute stereochemistry was determined via chemical derivatization and comparison with a known compound, (6R,11R,12R,14R)-colletodiol. Additionally, halosmysin A was shown to be very potent against murine P388 leukemia, human HL-60 leukemia, and murine L1210 leukemia cell lines, with IC50 values ranging from 2.2 \u00b1 3.1 to 11.7 \u00b1 2.8 \u03bcM.<\/jats:p>","DOI":"10.3390\/md18060320","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T11:00:56Z","timestamp":1592478056000},"page":"320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Halosmysin A, a Novel 14-Membered Macrodiolide Isolated from the Marine-Algae-Derived Fungus Halosphaeriaceae sp."],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8591-7525","authenticated-orcid":false,"given":"Takeshi","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Medicinal Molecular Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruka","family":"Kogure","sequence":"additional","affiliation":[{"name":"Department of Medicinal Molecular Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minami","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Department of Medicinal Molecular Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8832-5720","authenticated-orcid":false,"given":"Takashi","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Molecular Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoya","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Medicinal Molecular Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nicoletti, R., and Vinale, F. (2018). Bioactive Compounds from Marine-Derived Aspergillus, Penicillium, Talaromyces and Trichoderma Species. Mar. Drugs, 16.","DOI":"10.3390\/md16110408"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Imhoff, J.F. (2016). Natural Products from Marine Fungi\u2014Still an Underrepresented Resource. Mar. Drugs, 14.","DOI":"10.3390\/md14010019"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1039\/C6NP00124F","article-title":"Marine natural products","volume":"34","author":"Blunt","year":"2017","journal-title":"Nat. Prod. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1039\/C7NP00052A","article-title":"Marine natural 369 products","volume":"35","author":"Blunt","year":"2018","journal-title":"Nat. Prod. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4146","DOI":"10.1021\/jo100496f","article-title":"The relationship between the CD Cotton effect and the absolute configuration of FD-838 and its seven stereoisomers","volume":"75","author":"Yamada","year":"2010","journal-title":"J. Org. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"MacMillan, J., and Simpson, T.J. (1973). Fungal Products. Part V. The absolute stereochemistry of colletodiol and the structures of related metabolites of Colletotrichum capsici. J. Chem. Soc. Perkin Trans. 1, 1487\u20131493.","DOI":"10.1039\/p19730001487"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S0040-4039(00)71444-4","article-title":"Grahamimycin A1: A novel dilactone antibiotic from Cytospora","volume":"21","author":"Ronald","year":"1980","journal-title":"Tetrahedron Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1128\/AAC.19.1.153","article-title":"Grahamimycins: Antibiotics from Cytospora sp. Ehrenb. W.F.P.L. 13A","volume":"19","author":"Gurusiddaiah","year":"1981","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hanson, K., O\u2019neill, J.A., Simpson, T.J., and Willis, C.L. (1994). Bartanol and bartallol, novel macrodiolides from Cytospora sp. ATCC 20502. J. Chem. Soc. Perkin Trans. 1, 2493\u20132497.","DOI":"10.1039\/p19940002493"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"H\u00f6ller, U., K\u00f6nig, G.M., and Wright, A.D. (1999). A new tyrosine kinase inhibitor from a marine isolate of Ulocladium botrytis and new metabolites from the marine fungi Asteromyces cruciatus and Varicosporina ramulosa. Eur. J. Org. Chem., 2949\u20132955.","DOI":"10.1002\/(SICI)1099-0690(199911)1999:11<2949::AID-EJOC2949>3.3.CO;2-P"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"343","DOI":"10.7164\/antibiotics.46.343","article-title":"Secondary metabolites by Chemical screening. 21 Clonostachydiol, a novel anthelmintic macrolide from the fungus Clonostachys cylindrospora (strain FH-A 6607)","volume":"46","author":"Grabley","year":"1992","journal-title":"J. Antibiot."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1021\/np0504917","article-title":"Bioactivity profiling using HPLC\/microtiter-plate analysis: Application to a New Zealand marine alga-derived fungus, Gliocladium sp.","volume":"69","author":"Lang","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41429-017-0008-9","article-title":"Cordybislactone, a stereoisomer of the 14-membered bislactoneclonostachydiol, from the hopper pathogenic fungus Cordyceps sp. BCC 49294: Revision of the absolute configuration of clonostachydiol","volume":"71","author":"Ojima","year":"2018","journal-title":"J. Antibiot."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1021\/np100873t","article-title":"Ring B aromatic norpimarane glucoside from a Xylaria sp.","volume":"74","author":"Isaka","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3930","DOI":"10.1021\/jo900370a","article-title":"Asymmetric total synthesis and revision of the absolute configuration of 4-Keto-clonostachydiol","volume":"74","author":"Han","year":"2009","journal-title":"J. Org. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"660","DOI":"10.7164\/antibiotics.55.660","article-title":"Acremonol and acremodiol, new fungal bislactones","volume":"55","author":"Berg","year":"2002","journal-title":"J. Antibiot."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1021\/acs.orglett.7b03949","article-title":"Acaulide, an osteogenic macrodiolide from Acaulium sp. H-JQSF, an isopod-associated fungus","volume":"20","author":"Wang","year":"2018","journal-title":"Org. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1002\/hlca.19810640609","article-title":"Revidierte struktur des makrodiolids colletodiol","volume":"6","author":"Amstutz","year":"1981","journal-title":"Helv. Chim. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4687","DOI":"10.1016\/j.tetlet.2017.11.001","article-title":"Formal synthesis of 14-membered unsymmetrical bis-macrolactone, (\u2013)-colletodiol","volume":"58","author":"Khomane","year":"2017","journal-title":"Tetrahedron Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0040-4039(94)02195-H","article-title":"Studies directed towards the synthesis of clonostachydiol-Part I","volume":"36","author":"Rao","year":"1995","journal-title":"Tetrahedron Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0040-4039(94)02196-I","article-title":"The first synthesis and determination of absolute stereochemistry of clonostachydiol-Part II","volume":"36","author":"Rao","year":"1995","journal-title":"Tetrahedron Lett."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yadav, J.S., Swamy, T., and Subba Reddy, B.V. (2008). A stereoselective approach for the total synthesis of clonostachydiol. Synlett, 2773\u20132776.","DOI":"10.1055\/s-0028-1087296"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.tetasy.2012.01.014","article-title":"Stereoselective total synthesis of clonostachydiol","volume":"23","author":"Ramulu","year":"2012","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1016\/S0040-4039(00)60393-3","article-title":"Two novel diketopiperazines isolated from the fungus Tolypocladium sp.","volume":"34","author":"Chu","year":"1993","journal-title":"Tetrahedron Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"655","DOI":"10.7164\/antibiotics.55.655","article-title":"New dioxopiperazine metabolites from a Fusarium species separated from a marine alga","volume":"55","author":"Usami","year":"2002","journal-title":"J. Antibiot."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.phytochem.2010.05.012","article-title":"Diketopiperazines produced by endophytic fungi found in association with two Asteraceae species","volume":"71","author":"Guimaraes","year":"2010","journal-title":"Phytochemisry"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Salvatore, M.M., Nicoletti, R., DellaGreca, M., and Andolfi, A. (2019). Occurrence and properties of thiosilvatins. Mar. Drugs, 17.","DOI":"10.3390\/md17120664"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Simpson, T.J., and Stevenson, G.I. (1985). Studies of polyketide chain-assembly processes: Origins of the hydrogen and oxygen atoms in colletodiol. J. Chem. Soc. Chem. Commun., 1822\u20131824.","DOI":"10.1039\/c39850001822"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"O\u2019neill, J.A., Simpson, T.J., and Willis, C.L. (1993). Biosynthesis of colletodiol and related polyketide macrodiolides in Cytospora sp. ATCC 20502: Synthesis and metabolism of advanced intermediates. J. Chem. Soc. Chem. Commun., 738\u2013740.","DOI":"10.1039\/c39930000738"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/18\/6\/320\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:40:14Z","timestamp":1760175614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/18\/6\/320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,18]]},"references-count":29,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["md18060320"],"URL":"https:\/\/doi.org\/10.3390\/md18060320","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,18]]}}}