{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:31:09Z","timestamp":1790541069362,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI078376"],"award-info":[{"award-number":["R21AI078376"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1RC2AT005917"],"award-info":[{"award-number":["1RC2AT005917"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Harbor Branch Oceanographic Institute Foundation","award":["Research Excellence"],"award-info":[{"award-number":["Research Excellence"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Novel drug leads for malaria therapy are urgently needed because of the widespread emergence of resistance to all available drugs. Screening of the Harbor Branch enriched fraction library against the Plasmodium falciparum chloroquine-resistant strain (Dd2) followed by bioassay-guided fractionation led to the identification of two potent antiplasmodials; a novel diterpene designated as bebrycin A (1) and the known C21 degraded terpene nitenin (2). A SYBR Green I assay was used to establish a Dd2 EC50 of 1.08 \u00b1 0.21 and 0.29 \u00b1 0.02 \u00b5M for bebrycin A and nitenin, respectively. Further analysis was then performed to assess the stage specificity of the inhibitors antiplasmodial effects on the Dd2 intraerythrocytic life cycle. Exposure to bebrycin A was found to block parasite maturation at the schizont stage if added any time prior to late schizogony at 42 hours post invasion, (HPI). In contrast, early life cycle exposure to nitenin (prior to 18 HPI) was identified as crucial to parasite inhibition, suggesting nitenin may target the maturation of the parasite during the transition from ring to early trophozoite (6\u201318 HPI), a novel property among known antimalarials.<\/jats:p>","DOI":"10.3390\/md19040179","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T14:51:12Z","timestamp":1616683872000},"page":"179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Antiplasmodial Compounds from Deep-Water Marine Invertebrates"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4872-9776","authenticated-orcid":false,"given":"Amy E.","family":"Wright","sequence":"first","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1195-4630","authenticated-orcid":false,"given":"Jennifer E.","family":"Collins","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32826, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bracken","family":"Roberts","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32826, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill C.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla L.","family":"Winder","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K.","family":"Reed","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Diaz","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley A.","family":"Pomponi","sequence":"additional","affiliation":[{"name":"Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US Highway 1 North, Fort Pierce, FL 34946, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4554-3119","authenticated-orcid":false,"given":"Debopam","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32826, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(12)60034-8","article-title":"Global malaria mortality between 1980 and 2010: A systematic analysis","volume":"379","author":"Murray","year":"2012","journal-title":"Lancet"},{"key":"ref_2","unstructured":"WHO (2020, December 15). World Malaria Report. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240015791."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"d2793","DOI":"10.1136\/bmj.d2793","article-title":"WHO urges the phasing out of artemisinin based monotherapy for malaria to reduce resistance","volume":"342","author":"Cui","year":"2011","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1314981","article-title":"Spread of artemisinin resistance in Plasmodium falciparum malaria","volume":"371","author":"Ashley","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.pt.2016.05.010","article-title":"Artemisinin Action and Resistance in Plasmodium falciparum","volume":"32","author":"Tilley","year":"2016","journal-title":"Trends Parasitol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12936-015-1075-7","article-title":"Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa","volume":"15","author":"Slater","year":"2016","journal-title":"Malar. J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Duru, V., Khim, N., Leang, R., Kim, S., Domergue, A., Kloeung, N., Ke, S., Chy, S., Eam, R., and Khean, C. (2015). Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: Retrospective and prospective investigations. BMC Med., 13.","DOI":"10.1186\/s12916-015-0539-5"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"561","DOI":"10.4062\/biomolther.2016.181","article-title":"Marine-Derived Pharmaceuticals\u2014Challenges and Opportunities","volume":"24","author":"Lindequist","year":"2016","journal-title":"Biomol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Alvarez-Bardon, M., Perez-Pertejo, Y., Ordonez, C., Sepulveda-Crespo, D., Carballeira, N.M., Tekwani, B.L., Murugesan, S., Martinez-Valladares, M., Garcia-Estrada, C., and Reguera, R.M. (2020). Screening Marine Natural Products for New Drug Leads against Trypanosomatids and Malaria. Mar. Drugs, 18.","DOI":"10.3390\/md18040187"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00743-17","DOI":"10.1128\/AAC.00743-17","article-title":"Selective Killing of Dormant Mycobacterium tuberculosis by Marine Natural Products","volume":"61","author":"Rodrigues","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1128\/AAC.02091-12","article-title":"The bis(indolyl)imidazole alkaloid nortopsentin A exhibits antiplasmodial activity","volume":"57","author":"Alvarado","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","unstructured":"Chakrabarti, D., and Wright, A. (2014). Screening Methods for Identifying Anti-Malarial Compounds from Marine Natural Products and Methods of Use Thereof for Treating Malaria. (US20140200226), U.S. Patent."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1016\/S0040-4020(01)98252-3","article-title":"Isolation and structure of nitenin and dihydronitenin, new furanoterpenes from Spongia nitens","volume":"27","author":"Fattorusso","year":"1971","journal-title":"Tetrahedron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1021\/np9600964","article-title":"Structural and Stereochemical Studies of C-21 Terpenoids from Mediterranean Spongiidae Sponges","volume":"59","author":"Fontana","year":"1996","journal-title":"J. Nat. Prod."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kamada, T., Kang, M.-C., Phan, C.-S., Zanil, I.I., Jeon, Y.-J., and Vairappan, C.S. (2018). Bioactive cembranoids from the soft coral genus Sinularia sp. in Borneo. Mar. Drugs, 16.","DOI":"10.3390\/md16040099"},{"key":"ref_16","unstructured":"Stothers, J.B. (1972). Carbon-13 NMR Spectroscopy (Organic Chemistry: A Series of Monographs, Vol. 24), Academic Press."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1128\/AAC.01881-12","article-title":"Defining the timing of action of antimalarial drugs against Plasmodium falciparum","volume":"57","author":"Wilson","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3839\/jabc.2013.008","article-title":"Analysis of carotenoids in 25 indigenous Korean coral extracts","volume":"56","author":"Kim","year":"2013","journal-title":"J. Appl. Biol. Chem."},{"key":"ref_19","first-page":"154","article-title":"Bebrycoside, a new steroidal glycoside from the Chinese gorgonian coral Bebryce indica","volume":"62","author":"Yang","year":"2007","journal-title":"Pharmazie"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1021\/np980063j","article-title":"Bebryazulene, a New Guaiane Metabolite from the Indian Ocean Gorgonian Coral, Bebryce grandicalyx","volume":"61","author":"Aknin","year":"1998","journal-title":"J. Nat. Prod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9442","DOI":"10.1021\/acs.orglett.9b03654","article-title":"Characterization of Micromonocyclol Synthase from the Marine Actinomycete Micromonospora marina","volume":"21","author":"Rinkel","year":"2019","journal-title":"Org. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0305-0491(94)00250-X","article-title":"Chemical studies of Cadlina mollusks from the Cantabrian Sea (Atlantic Ocean)","volume":"111B","author":"Fontana","year":"1995","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Noyer, C., Thomas, O.P., and Becerro, M.A. (2011). Patterns of chemical diversity in the Mediterranean sponge Spongia lamella. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020844"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1021\/np970390b","article-title":"New metabolites from the sponge Spongia agaricina","volume":"61","author":"Rueda","year":"1998","journal-title":"J. Nat. Prod."},{"key":"ref_25","first-page":"125","article-title":"The Alcyonaria of the western part of the Atlantic Ocean","volume":"53","author":"Deichmann","year":"1936","journal-title":"Mem. Mus. Comp. Zool."},{"key":"ref_26","unstructured":"Bayer, F.M., and Cairns, S.D. (2004). The Unpublished Plates for A.E. Verrill\u2019s Unfinished Report on the Alcyonaria of the \u201cBlake\u201d Expeditions: With Revised Explanations of the Figures Transcribed from A.E. Verrill\u2019s Original Typescript."},{"key":"ref_27","first-page":"593","article-title":"Untersuchungen \u00fcber den Bau und die Entwicklung der Spongien. Siebente Mittheilung. Die Familie der Spongidae","volume":"32","author":"Schulze","year":"1879","journal-title":"Z. Wiss. Zool."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1439-0485.2008.00235.x","article-title":"Mediterranean commercial sponges: Over 5000 years of natural history and cultural heritage","volume":"29","author":"Pronzato","year":"2008","journal-title":"Mar. Ecol. Prog. Ser."},{"key":"ref_29","first-page":"477","article-title":"In vitro culture of Plasmodium parasites","volume":"72","author":"Jensen","year":"2002","journal-title":"Methods Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12020","DOI":"10.1073\/pnas.90.24.12020","article-title":"Cloning and characterization of subunit genes of ribonucleotide reductase, a cell-cycle-regulated enzyme, from Plasmodium falciparum","volume":"90","author":"Chakrabarti","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1128\/AAC.01607-06","article-title":"Assessment and continued validation of the malaria SYBR green I-based fluorescence assay for use in malaria drug screening","volume":"51","author":"Johnson","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1128\/AAC.48.5.1807-1810.2004","article-title":"Novel, rapid, and inexpensive cell-based quantification of antimalarial drug efficacy","volume":"48","author":"Bennett","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1128\/AAC.48.5.1803-1806.2004","article-title":"Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening","volume":"48","author":"Smilkstein","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ijpddr.2016.02.004","article-title":"Spirocyclic chromanes exhibit antiplasmodial activities and inhibit all intraerythrocytic life cycle stages","volume":"6","author":"Roberts","year":"2016","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/1475-2875-13-112","article-title":"Magnetic isolation of Plasmodium falciparum schizonts iRBCs to generate a high parasitaemia and synchronized in vitro culture","volume":"13","author":"Sanz","year":"2014","journal-title":"Malar. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"418","DOI":"10.2307\/3280287","article-title":"Synchronization of Plasmodium falciparum erythrocytic stages in culture","volume":"65","author":"Lambros","year":"1979","journal-title":"J. Parasitol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ijpddr.2017.02.002","article-title":"4-Nitro styrylquinoline is an antimalarial inhibiting multiple stages of Plasmodium falciparum asexual life cycle","volume":"7","author":"Roberts","year":"2017","journal-title":"Int. J. Parasitol. Drugs Drug Resist."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/4\/179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:40:49Z","timestamp":1760161249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/4\/179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,25]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["md19040179"],"URL":"https:\/\/doi.org\/10.3390\/md19040179","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,25]]}}}