{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:04:40Z","timestamp":1785423880805,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"crossref","award":["2016\/16223-7"],"award-info":[{"award-number":["2016\/16223-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"crossref","award":["2016\/06931-4"],"award-info":[{"award-number":["2016\/06931-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2016\/16223-7"],"award-info":[{"award-number":["2016\/16223-7"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2016\/06931-4"],"award-info":[{"award-number":["2016\/06931-4"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Schistosomiasis, a parasitic disease caused by Schistosoma worms with freshwater snails as intermediate hosts, affects over 250 million people. The current control relies solely on praziquantel, which raises concerns on drug resistance and highlights the need for new therapeutic alternatives. Our bioprospection studies have focused on marine macroalgae as an unexplored source of antischistosomal metabolites with promising results. Guided by WHO recommendations to target both the parasite and its transmission vectors, this study aimed to investigate Ochtodes secundiramea to: (i) isolate active metabolites; (ii) evaluate the isolated compounds against adult worms and oviposition to identify leads for drug development; and (iii) perform an independent screening of their effects against the environmental transmission stages on cercariae and B. glabrata embryos. Methods: A dichloromethane extract of O. secundiramea was submitted to an NMR\u2013biomonitored guided fractionation against Schistosoma mansoni adult worms. Active fractions were further purified through HPLC and characterized by 1H and 13C NMR spectroscopy to identify the isolated compounds. Results: Three halogenated monoterpenes were isolated: ochtodene 1 (4-bromo-1,6,8-trichloro-2,3-ochtodene), ochtodene 2 (2-chloro-1,6,8-tribromo-3,8-ochtodene), and the novel natural product ochtodene 3 [2,6-dibromo-4-(2-chloroethylidene)-1,1dimethylcyclohexane]. Ochtodene 1 was the primary active metabolite against Schistosoma mansoni adult worms, with IC50\/96 h values of 47.2 and 46.1 \u00b5M for male and female worms respectively, and totally suppressed egg laying with 60 \u00b5M, while showing no toxicity toward human fibroblasts. Notably, all metabolites, including the novel ochtodene 3, caused 100% mortality in cercariae and embryos at low concentrations. Conclusions: The discovery of the novel ochtodene 3 and the identification of distinct leads for host treatment and transmission elimination position O. secundiramea as a promising source for integrated schistosomiasis control.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070767","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:52:11Z","timestamp":1782453131000},"page":"767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Seaweed-Derived Halogenated Monoterpenes as Lead Compounds in Schistosomiasis Control"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3144-3344","authenticated-orcid":false,"given":"Sara Guibunda","family":"Taj\u00fa","sequence":"first","affiliation":[{"name":"Research Center in Biodiversity and Conservation\u2014CPBC, P\u00fangu\u00e8 University, Chimoio 333, Manica, Mozambique"},{"name":"Laboratory of Parasitology, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2479-5325","authenticated-orcid":false,"given":"Amanda Beatriz da Silva","family":"Soares","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitology, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Laboratory of Algae Biochemistry and Molecular Biology, Institute of Chemistry, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4871-5972","authenticated-orcid":false,"given":"Patr\u00edcia Aoki","family":"Miyasato","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitology, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-5605","authenticated-orcid":false,"given":"Rafaela Paula","family":"de Freitas","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitology, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9234-5158","authenticated-orcid":false,"given":"Lenita de Freitas","family":"Tallarico","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitology, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3309-1944","authenticated-orcid":false,"given":"Erika Mattos","family":"Stein","sequence":"additional","affiliation":[{"name":"Laboratory of Algae Biochemistry and Molecular Biology, Institute of Chemistry, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2334-1532","authenticated-orcid":false,"given":"Pio","family":"Colepicolo","sequence":"additional","affiliation":[{"name":"Laboratory of Algae Biochemistry and Molecular Biology, Institute of Chemistry, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-090, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7839-9600","authenticated-orcid":false,"given":"Eliana","family":"Nakano","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitology, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","unstructured":"(2026, March 08). World Health Organization (WHO). Available online: https:\/\/www.who.int\/health-topics\/schistosomiasis#tab=tab_1."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107504","DOI":"10.1016\/j.actatropica.2024.107504","article-title":"Global trends of schistosomiasis burden from 1990 to 2021 across 204 countries and territories: Findings from GBD 2021 study","volume":"261","author":"Li","year":"2025","journal-title":"Acta Trop."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/S0140-6736(06)69440-3","article-title":"Human schistosomiasis","volume":"368","author":"Gryseels","year":"2006","journal-title":"Lancet"},{"key":"ref_4","unstructured":"Ntuli, D.M.M. (2020). Control of Neglected Tropical Diseases (NTD), WHO."},{"key":"ref_5","unstructured":"World Health Organization (WHO) (2017). Global Vector Control Response 2017\u20132030, WHO."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Stein, E.M., Taj\u00fa, S.G., Miyasato, P.A., de Freitas, R.P., Tallarico, L.F., Dos Santos, G.S., Luiz, G.L.F., Rofatto, H.K., da Silva, F.N.V., and Colepicolo, P. (2021). The Prospective Use of Brazilian Marine Macroalgae in Schistosomiasis Control. Mar. Drugs, 19.","DOI":"10.3390\/md19050234"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s10811-018-1572-5","article-title":"Bioactive compounds against neglected diseases isolated from macroalgae: A review","volume":"31","author":"Falkenberg","year":"2018","journal-title":"J. Appl. Phycol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1021\/acs.jnatprod.3c00803","article-title":"A Survey of Recently Discovered Naturally Occurring Organohalogen Compounds","volume":"87","author":"Gribble","year":"2024","journal-title":"J. Nat. Prod."},{"key":"ref_9","first-page":"189","article-title":"Chemical and Biological Aspects of Marine Monoterpenes","volume":"Volume 44","author":"Naylor","year":"1983","journal-title":"Fortschritte der Chemie Organischer Naturstoffe\/Progress in the Chemistry of Organic Natural Products"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S1389-0344(03)00054-6","article-title":"Metabolic flux analysis of halogenated monoterpene biosynthesis in microplantlets of the macrophytic red alga Ochtodes secundiramea","volume":"20","author":"Polzin","year":"2003","journal-title":"Biomol. Eng."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/S0031-9422(00)80451-3","article-title":"2-chloro-1,6(S*),8-tribromo-3-(8)(Z)-ochtodene: A metabolite of the tropical red seaweed Ochtodes secundiramea","volume":"23","author":"Gerwick","year":"1984","journal-title":"Phytochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"dos Santos, G.S., Miyasato, P.A., Stein, E.M., Colepicolo, P., Wright, A.D., Pereira, C.A.B., Falkenberg, M., and Nakano, E. (2022). Algal-Derived Halogenated Sesquiterpenes from Laurencia dendroidea as Lead Compounds in Schistosomiasis Environmental Control. Mar. Drugs, 20.","DOI":"10.3390\/md20020111"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Waksmundzka-Hajnos, M., Sherma, J., and Kowalska, T. (2008). Thin Layer Chromatography in Phytochemistry, CRC Press. [1st ed.].","DOI":"10.1201\/9781420046786"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.bjp.2015.09.005","article-title":"Antischistosomal activity from Brazilian marine algae","volume":"25","author":"Stein","year":"2015","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2307\/3280632","article-title":"Cultivation of Schistosoma mansoni in vitro. I. Establishment of cultures from cercariae and development until pairing","volume":"67","author":"Basch","year":"1981","journal-title":"J. Parasitol."},{"key":"ref_16","first-page":"388","article-title":"Probit Analysis (2nd ed.)","volume":"78","author":"Finney","year":"1952","journal-title":"J. Inst. Actuar."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1021\/jm00094a012","article-title":"A pentahalogenated monoterpene from the red alga Portieria hornemannii produces a novel cytotoxicity profile against a diverse panel of human tumor cell lines","volume":"35","author":"Fuller","year":"1992","journal-title":"J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.1021\/jo00415a056","article-title":"Ochtodene and ochtodiol: Novel polyhalogenated cyclic monoter-penes from the red seaweed Ochtodes secundiramea","volume":"43","author":"McConnell","year":"1978","journal-title":"J. Org. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102330","DOI":"10.1016\/j.algal.2021.102330","article-title":"Update on sesquiterpenes from red macroalgae of the Laurencia genus and their biological activities (2015\u20132020)","volume":"56","author":"Jurin","year":"2021","journal-title":"Algal Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0022-0981(88)90141-4","article-title":"Chemical defense in the seaweed Ochtodes secundiramea (Montagne) Howe (Rhodophyta): Effects of its monoterpenoid components upon diverse coral-reef herbivores","volume":"114","author":"Paul","year":"1988","journal-title":"J. Exp. Mar. Biol. Ecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1021\/np50072a041","article-title":"A new polyhalogenated monoterpene from the red alga Plocamium cartilagineum","volume":"53","author":"Wright","year":"1990","journal-title":"J. Nat. Prod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1007\/s10637-011-9788-0","article-title":"Quinones and halogenated monoterpenes of algal origin show anti-proliferative effects against breast cancer cells in vitro","volume":"30","author":"Lawson","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.1021\/jm00051a019","article-title":"Isolation and structure\/activity features of halomon-related antitumor monoterpenes from the red alga Portieria hornemannii","volume":"37","author":"Fuller","year":"1994","journal-title":"J. Med. Chem."},{"key":"ref_24","unstructured":"Ali, S.M., Allan, F., Ayi, I., Chandre, F., Coelho, P.M.Z., El-Hawary, A.K., Jiamrong, D., Kariuki, C., N\u2019Goran, E.K., and Madsen, H. (2017). Field Use of Molluscicides in Schistosomiasis Control Programmes: An Operational Manual for Programmemanagers, World Health Organization."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ecoenv.2014.09.005","article-title":"Developmental toxicity, acute toxicity and mutagenicity testing in freshwater snails Biomphalaria glabrata (Mollusca: Gastropoda) exposed to chromium and water samples","volume":"110","author":"Borrely","year":"2014","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.rmb.2016.01.017","article-title":"The role of Phyllocaulis variegatus (Mollusca: Veronicellidae) in the transmission of digenean parasites","volume":"87","author":"Valente","year":"2016","journal-title":"Rev. Mex. Biodivers."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s41182-020-00205-y","article-title":"Ethnopharmacological evaluation of schistosomicidal and cercaricidal activities of some selected medicinal plants from Ghana","volume":"48","author":"Acheampong","year":"2020","journal-title":"Trop. Med. Health"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kamel, B., Laidemitt, M.R., Lu, L., Babbitt, C., Weinbaum, O.L., Mkoji, G.M., and Loker, E.S. (2021). Detecting and identifying Schistosoma infections in snails and aquatic habitats: A systematic review. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009175"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1590\/S0102-695X2009000200005","article-title":"Evaluation of the molluscicidal and Schistosoma mansoni cercariae activity of Croton floribundus extracts and kaurenoic acid","volume":"19","author":"Medina","year":"2009","journal-title":"Rev. Bras. Farm."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/7\/767\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:33:59Z","timestamp":1783053239000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/7\/767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["pharmaceutics18070767"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18070767","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}