{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:47:43Z","timestamp":1768913263769,"version":"3.49.0"},"reference-count":72,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-SC1 Program","award":["1SC1GM086271-01A1"],"award-info":[{"award-number":["1SC1GM086271-01A1"]}]},{"name":"NIH-SC1 Program","award":["U54MD007600"],"award-info":[{"award-number":["U54MD007600"]}]},{"name":"National Institute of Minority Health and Health Disparities RCMI","award":["1SC1GM086271-01A1"],"award-info":[{"award-number":["1SC1GM086271-01A1"]}]},{"name":"National Institute of Minority Health and Health Disparities RCMI","award":["U54MD007600"],"award-info":[{"award-number":["U54MD007600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Plakortinic acids C (1) and D (2), an unseparable pair of endoperoxide polyketides isolated and purified from the symbiotic association of Caribbean Sea sponges Plakortis symbiotica-Xestospongia deweerdtae, underwent in vitro evaluation for antiplasmodial activity against the malaria parasite Plasmodium berghei using a drug luminescence assay. Initial screening at 10 \u00b5M revealed 50% in vitro parasite growth inhibition. The title compounds displayed antiplasmodial activity with an EC50 of 5.3 \u00b5M toward P.\u00a0berghei parasites. The lytic activity against erythrocytes was assessed through an erythrocyte cell lysis assay, which showed non-lytic activity at lower concentrations ranging from 1.95 to 3.91 \u00b5M. The antiplasmodial activity and the absence of hemolytic activity support the potential of plakortinic acids C (1) and D (2) as promising lead compounds. Moreover, drug-likeness (ADMET) properties assessed through the pkCSM server predicted high intestinal absorption, hepatic metabolism, and volume of distribution, indicating favorable pharmacokinetic profiles for oral administration. These findings suggest the potential suitability of these metabolites for further investigations of antiplasmodial activity in multiple parasitic stages in the mosquito and Plasmodium falciparum. Notably, this study represents the first report of a marine natural product exhibiting the unique 7,8-dioxatricyclo[4.2.2.02,5]dec-9-ene motif being evaluated against malaria.<\/jats:p>","DOI":"10.3390\/life14060684","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T10:14:07Z","timestamp":1716804847000},"page":"684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Probing the Antiplasmodial Properties of Plakortinic Acids C and D: An Uncommon Pair of Marine Peroxide-Polyketides Isolated from a Two-Sponge Association of Plakortis symbiotica and Xetospongia deweerdtae Collected near Puerto Rico"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2456-0171","authenticated-orcid":false,"given":"Luis A.","family":"Amador","sequence":"first","affiliation":[{"name":"Molecular Sciences Research Center, University of Puerto Rico, 1390 Ponce de Le\u00f3n Avenue, San Juan 00926, Puerto Rico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilee E.","family":"Col\u00f3n-Lorenzo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Medical Zoology, University of Puerto Rico School of Medicine, San Juan 00921, Puerto Rico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abimael D.","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Molecular Sciences Research Center, University of Puerto Rico, 1390 Ponce de Le\u00f3n Avenue, San Juan 00926, Puerto Rico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelfa E.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Medical Zoology, University of Puerto Rico School of Medicine, San Juan 00921, Puerto Rico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4670","DOI":"10.1111\/j.1742-4658.2007.05997.x","article-title":"Malaria\u2014An Overview","volume":"274","author":"Tuteja","year":"2007","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.cell.2016.07.055","article-title":"Malaria: Biology and Disease","volume":"167","author":"Cowman","year":"2016","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Talapko, J., \u0160krlec, I., Alebi\u0107, T., Juki\u0107, M., and V\u010dev, A. 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