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The available treatments against these parasitic diseases are limited and display multiple undesired effects. The brown alga belonging to the genus Gongolaria has been previously reported as a source of compounds with different biological activities. In a recent study from our group, Gongolaria abies-marine was proven to present antiamebic activity. Hence, this brown alga could be a promising source of interesting molecules for the development of new antiprotozoal drugs. In this study, four meroterpenoids were isolated and purified from a dichloromethane\/ethyl acetate crude extract through a bioguided fractionation process targeting kinetoplastids. Moreover, the in vitro activity and toxicity were evaluated, and the induction of programmed cell death was checked in the most active and less toxic compounds, namely gongolarone B (2), 6Z-1\u2032-methoxyamentadione (3) and 1\u2032-methoxyamentadione (4). These meroterpenoids triggered mitochondrial malfunction, oxidative stress, chromatin condensation and alterations of the tubulin network. Furthermore, a transmission electron microscopy (TEM) image analysis showed that meroterpenoids (2\u20134) induced the formation of autophagy vacuoles and ER and Golgi complex disorganization. The obtained results demonstrated that the mechanisms of action at the cellular level of these compounds were able to induce autophagy as well as an apoptosis-like process in the treated parasites.<\/jats:p>","DOI":"10.3390\/ph16040476","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T03:07:57Z","timestamp":1679540877000},"page":"476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Meroterpenoids from Gongolaria abies-marina against Kinetoplastids: In Vitro Activity and Programmed Cell Death Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6622-1928","authenticated-orcid":false,"given":"Desir\u00e9e San","family":"Nicol\u00e1s-Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda. Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38206 La Laguna, Tenerife, Spain"},{"name":"Departamento de Obstetricia y Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38206 La Laguna, Tenerife, Spain"},{"name":"Red de Investigaci\u00f3n Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3858-836X","authenticated-orcid":false,"given":"Rub\u00e9n L.","family":"Rodr\u00edguez-Exp\u00f3sito","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda. Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38206 La Laguna, Tenerife, Spain"},{"name":"Departamento de Obstetricia y Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38206 La Laguna, Tenerife, Spain"},{"name":"Red de Investigaci\u00f3n Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0675-8221","authenticated-orcid":false,"given":"Atteneri","family":"L\u00f3pez-Arencibia","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda. Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38206 La Laguna, Tenerife, Spain"},{"name":"Departamento de Obstetricia y Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38206 La Laguna, Tenerife, Spain"},{"name":"Red de Investigaci\u00f3n Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos J.","family":"Bethencourt-Estrella","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda. Astrof\u00edsico Fco. S\u00e1nchez, S\/N, 38206 La Laguna, Tenerife, Spain"},{"name":"Departamento de Obstetricia y Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38206 La Laguna, Tenerife, Spain"},{"name":"Red de Investigaci\u00f3n Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Sifaoui","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda. Astrof\u00edsico Fco. 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Astrof\u00edsico Fco. S\u00e1nchez 3, 38206 La Laguna, Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana R.","family":"D\u00edaz-Marrero","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Bio-Org\u00e1nica Antonio Gonz\u00e1lez, Departamento de Qu\u00edmica Org\u00e1nica, Universidad de La Laguna, Avda. Astrof\u00edsico Fco. S\u00e1nchez 3, 38206 La Laguna, Tenerife, Spain"},{"name":"Instituto de Productos Naturales y Agrobiolog\u00eda, Consejo Superior de Investigaciones Cient\u00edficas, Avda. Astrof\u00edsico Fco. S\u00e1nchez 3, 38206 La Laguna, Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6233-8224","authenticated-orcid":false,"given":"Jos\u00e9 E.","family":"Pi\u00f1ero","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Enfermedades Tropicales y Salud P\u00fablica de Canarias, Universidad de La Laguna, Avda. Astrof\u00edsico Fco. 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S\u00e1nchez, S\/N, 38206 La Laguna, Tenerife, Spain"},{"name":"Departamento de Obstetricia y Ginecolog\u00eda, Pediatr\u00eda, Medicina Preventiva y Salud P\u00fablica, Toxicolog\u00eda, Medicina Legal y Forense y Parasitolog\u00eda, Universidad de La Laguna, 38206 La Laguna, Tenerife, Spain"},{"name":"Red de Investigaci\u00f3n Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, 28006 Madrid, Spain"},{"name":"Consorcio Centro de Investigaci\u00f3n Biom\u00e9dica En Red (CIBER) de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023, January 07). Neglected Tropical Diseases. Available online: https:\/\/www.who.int\/news-room\/q-a-detail\/neglected-tropical-diseases."},{"key":"ref_2","unstructured":"WHO (2023, January 07). Leishmaniasis. Available online: https:\/\/www.who.int\/es\/news-room\/fact-sheets\/detail\/leishmaniasis."},{"key":"ref_3","unstructured":"WHO (2023, January 07). Chagas Disease (American Trypanosomiasis). Available online: https:\/\/www.who.int\/health-topics\/chagas-disease#tab=tab_1."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.pt.2019.10.002","article-title":"Trypanosoma cruzi","volume":"36","author":"Moretti","year":"2020","journal-title":"Trends Parasitol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"174","DOI":"10.2174\/156802661903190328155136","article-title":"Leishmaniasis and Chagas disease\u2014Neglected tropical diseases: Treatment updates","volume":"19","author":"Sangenito","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Reece, S.E., Pollitt, L.C., Colegrave, N., and Gardner, A. (2011). The meaning of death: Evolution and ecology of apoptosis in protozoan parasites. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002320"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41419-019-1370-2","article-title":"Cell death pathways in pathogenic trypanosomatids: Lessons of (over) kill","volume":"10","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40249-021-00796-6","article-title":"Potentials of marine natural products against malaria, leishmaniasis, and trypanosomiasis parasites: A review of recent articles","volume":"10","author":"Nweze","year":"2021","journal-title":"Infect. Dis. Poverty."},{"key":"ref_9","unstructured":"(2023, January 19). AlgaeBase. Available online: http:\/\/www.algaebase.org."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y11-093","article-title":"Antioxidant, anti-inflammatory, and antiproliferative activities of organic fractions from the Mediterranean brown seaweed Cystoseira sedoides","volume":"89","author":"Mhadhebi","year":"2011","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4067\/S0716-97602010000100005","article-title":"Cytotoxic activity of some marine brown algae against cancer cell lines","volume":"43","author":"Khanavi","year":"2010","journal-title":"Biol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lopes, G., Pinto, E., Andrade, P.B., and Valent\u00e3o, P. (2013). Antifungal activity of phlorotannins against dermatophytes and yeasts: Approaches to the mechanism of action and influence on Candida albicans virulence factor. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072203"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exppara.2017.01.002","article-title":"Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata","volume":"174","author":"Gangadhar","year":"2017","journal-title":"Exp. Parasitol."},{"key":"ref_14","first-page":"8332","article-title":"Antimicrobial and antiviral activities against Newcastle disease virus (NDV) from marine algae isolated from Qusier and Marsa-Alam seashore (Red Sea)","volume":"11","author":"Ibraheem","year":"2012","journal-title":"Egypt. Afr. J. Biotech."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1002\/ptr.3208","article-title":"Antimycobacterial, antiprotozoal and cytotoxic potential of twenty-one brown algae (Phaeophyceae) from British and Irish Waters","volume":"24","author":"Spavieri","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114185","DOI":"10.1016\/j.biopha.2022.114185","article-title":"Gongolarones as antiamoeboid chemical scaffold","volume":"158","author":"Sifaoui","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chiboub, O., Sifaoui, I., Lorenzo-Morales, J., Abderrabba, M., Mejri, M., Fern\u00e1ndez, J.J., Pi\u00f1ero, J.E., and D\u00edaz-Marrero, A.R. (2019). Spiralyde A, an antikinetoplastid dolabellane from the brown alga Dictyota spiralis. Mar. Drugs., 17.","DOI":"10.3390\/md17030192"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lorenzo-Morales, J., D\u00edaz-Marrero, A.R., Cen-Pacheco, F., Sifaoui, I., Reyes-Batlle, M., Souto, M.L., Hern\u00e1ndez Daranas, A., Pi\u00f1ero, J.E., and Fern\u00e1ndez, J.J. (2019). Evaluation of oxasqualenoids from the red alga Laurencia viridis against Acanthamoeba. Mar. Drugs., 17.","DOI":"10.3390\/md17070420"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nazir, M., Saleem, M., Tousif, M.I., Anwar, M.A., Surup, F., Ali, I., Wang, D., Mamadalieva, N.Z., Alshammari, E., and Ashour, M.L. (2021). Meroterpenoids: A comprehensive update insight on structural diversity and biology. Biomolecules, 11.","DOI":"10.3390\/biom11070957"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zbakh, H., Zub\u00eda, E., Reyes, C.L., Calder\u00f3n-Monta\u00f1o, J.M., and Motilva, V. (2020). Anticancer activities of meroterpenoids isolated from the brown alga Cystoseira usneoides against the human colon cancer cells HT-29. Foods., 9.","DOI":"10.3390\/foods9030300"},{"key":"ref_21","first-page":"71","article-title":"Assays related to cancer drug discovery","volume":"Volume 6","author":"Hostettmann","year":"1991","journal-title":"Methods in Plant Biochemistry: Assays for Bioactivity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"185918","DOI":"10.1093\/ecam\/nep014","article-title":"Brazilian green propolis: Effects in vitro and in vivo on Trypanosoma cruzi","volume":"2011","author":"Barbosa","year":"2011","journal-title":"J. Evid. Based Complement. Altern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1080\/14786419.2018.1434637","article-title":"Report of in vitro antileishmanial properties of Iberian macroalgae","volume":"33","author":"Lago","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ijantimicag.2004.08.010","article-title":"In vitro activity of C20-diterpenoid alkaloid derivatives in promastigotes and intracellular amastigotes of Leishmania infantum","volume":"25","author":"Hitos","year":"2005","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"583834","DOI":"10.3389\/fmicb.2021.583834","article-title":"PF-429242, a subtilisin inhibitor, is effective in vitro against Leishmania infantum","volume":"12","author":"Machado","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bomba\u00e7a, A.C.S., Dossow, D.V., Barbosa, J.M.C., Paz, C., Burgos, V., and Menna-Barreto, R.F.S. (2018). Trypanocidal activity of natural sesquiterpenoids involves mitochondrial dysfunction, ROS production and autophagic phenotype in Trypanosoma cruzi. Molecules, 23.","DOI":"10.3390\/molecules23112800"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.ejmech.2017.12.052","article-title":"Efficacy of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinone derivatives against different Trypanosoma cruzi discrete type units: Identification of a promising hit compound","volume":"144","author":"Lara","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s13071-021-04693-7","article-title":"Apoptosis-like cell death upon kinetoplastid induction by compounds isolated from the brown algae Dictyota spiralis","volume":"14","author":"Chiboub","year":"2021","journal-title":"Parasites Vectors"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"587685","DOI":"10.3389\/fcell.2020.587685","article-title":"Emerging functions of actins and actin binding proteins in trypanosomatids","volume":"8","author":"Gupta","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"114191","DOI":"10.1016\/j.bcp.2020.114191","article-title":"Histone deacetylases inhibitors as new potential drugs against Leishmania braziliensis, the main causative agent of new world tegumentary leishmaniasis","volume":"180","author":"Heimburg","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.pt.2019.07.008","article-title":"More than microtubules: The structure and function of the subpellicular array in trypanosomatids","volume":"35","author":"Sinclair","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1242\/jcs.111.5.597","article-title":"Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi","volume":"111","author":"Engel","year":"1998","journal-title":"J. Cell Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ijpddr.2021.01.003","article-title":"The ultimate fate determinants of drug induced cell-death mechanisms in Trypanosomatids","volume":"15","author":"Das","year":"2021","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/10575639808048304","article-title":"Novel metabolites from the brown alga Cystoseira abies-marina","volume":"12","author":"Navarro","year":"1998","journal-title":"Nat. Prod. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bethencourt-Estrella, C.J., Delgado-Hern\u00e1ndez, S., L\u00f3pez-Arencibia, A., San Nicol\u00e1s-Hern\u00e1ndez, D., Sifaoui, I., Tejedor, D., Garc\u00eda-Tellado, F., Lorenzo-Morales, J., and Pi\u00f1ero, J.E. (2021). Acrylonitrile derivatives against Trypanosoma cruzi: In vitro activity and programmed cell death study. Pharmaceuticals, 14.","DOI":"10.3390\/ph14060552"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e02127-16","DOI":"10.1128\/AAC.02127-16","article-title":"Perifosine mechanisms of action in Leishmania species","volume":"61","author":"Sifaoui","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cartuche, L., Sifaoui, I., L\u00f3pez-Arencibia, A., Bethencourt-Estrella, C.J., San Nicol\u00e1s-Hern\u00e1ndez, D., Lorenzo-Morales, J., Pi\u00f1ero, J.E., D\u00edaz-Marrero, A.R., and Fern\u00e1ndez, J.J. (2020). Antikinetoplastid activity of indolocarbazoles from Streptomyces sanyensis. Biomolecules, 10.","DOI":"10.3390\/biom10040657"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"110814","DOI":"10.1016\/j.biopha.2020.110814","article-title":"New phenalenone analogues with improved activity against Leishmania species","volume":"132","author":"Freijo","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Arencibia, A., San Nicol\u00e1s-Hern\u00e1ndez, D., Bethencourt-Estrella, C.J., Sifaoui, I., Reyes-Batlle, M., Rodr\u00edguez-Exp\u00f3sito, R.L., Rizo-Liendo, A., Lorenzo-Morales, J., Bazzocchi, I.L., and Pi\u00f1ero, J.E. (2019). Withanolides from Withania aristata as antikinetoplastid agents through induction of programmed cell death. Pathogens, 8.","DOI":"10.3390\/pathogens8040172"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1186\/s13071-019-3854-4","article-title":"In vitro activity of 1H-phenalen-1-one derivatives against Leishmania spp. and evidence of programmed cell death","volume":"12","author":"Freijo","year":"2019","journal-title":"Parasites Vectors"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110518","DOI":"10.1016\/j.biopha.2020.110518","article-title":"Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids","volume":"130","author":"Zeouk","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Castelan-Ram\u00edrez, I., Salazar-Villatoro, L., Ch\u00e1vez-Mungu\u00eda, B., Salinas-Lara, C., S\u00e1nchez-Garibay, C., Flores-Maldonado, C., Hern\u00e1ndez-Mart\u00ednez, D., Anaya-Mart\u00ednez, V., \u00c1vila-Costa, M.R., and M\u00e9ndez-Cruz, A.R. (2020). Schwann Cell autophagy and necrosis as mechanisms of cell death by Acanthamoeba. Pathogens, 9.","DOI":"10.3390\/pathogens9060458"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ejpb.2022.09.020","article-title":"Pitavastatin loaded nanoparticles: A suitable ophthalmic treatment for Acanthamoeba keratitis inducing cell death and autophagy in Acanthamoeba polyphaga","volume":"180","author":"Sifaoui","year":"2022","journal-title":"Eur. J. Pharm. Biopharm."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/4\/476\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:01:02Z","timestamp":1760122862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/4\/476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,23]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ph16040476"],"URL":"https:\/\/doi.org\/10.3390\/ph16040476","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,23]]}}}