{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T13:23:17Z","timestamp":1764940997955,"version":"3.46.0"},"reference-count":31,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministerio de Econom\u00eda, Industria y Competitividad"},{"name":"MAEC-AECID and project X.5 \u201cB\u00fasqueda, Obtenci\u00f3n y Evaluaci\u00f3n de Nuevos Agentes Antiparasitarios\u201d CYTED (Iberoamerican Program of Science and Technology for Development), Subprogram"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Given the known biological activity of both natural and synthetic substituted 1H-phenalen-1-ones, the generation of a small chemically and structurally diverse 1H-phenalen-1-one-based library of compounds was warranted. Herein, we have synthesized several groups of compounds to broaden and improve the chemical diversity of our 1H-phenalen-1-one collection. Additionally, we have also introduced hydroxyl, amides or carboxylic groups onto the core, or nitrogen atoms into the core, to increase the chemical diversity while also lowering the ClogP values to aid their water solubility. Notably, we have also improved the synthetic routes to several compounds of interest and have observed the unexpected formation of phenoxazine and acridin-7-one systems during cross-coupling reactions with polyfunctional anilines. Combining the compounds generated in this work with previous ones has enabled us to create a library of chemically diverse 1H-phenalen-1-one available for screening assays. Evaluation of anti-plasmodial activity against the chloroquine-resistant Plasmodium falciparum strain FCR3 revealed four compounds with notable activity, three of which exhibited IC50 values below 1 \u00b5M, while none displayed significant cytotoxicity at 10 \u00b5M.<\/jats:p>","DOI":"10.3390\/molecules30244667","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T13:17:07Z","timestamp":1764940627000},"page":"4667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis of Substituted 1H-Phenalen-1-ones and Nitrogen-Containing Heterocyclic Analogues as Potential Anti-Plasmodial Agents"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9674-7146","authenticated-orcid":false,"given":"Teresa","family":"Abad-Grillo","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Universidad de La Laguna, Avenida Astrof\u00edsico Francisco S\u00e1nchez, 2, 38206 La Laguna, Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant","family":"McNaughton-Smith","sequence":"additional","affiliation":[{"name":"Centro Atl\u00e1ntico del Medicamento S.A. (CEAMED S.A.), Parque Cient\u00edfico y Tecnol\u00f3gico de Tenerife (PCTT), 38200 La Laguna, Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica","family":"Blanco Freijo","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Universidad de La Laguna, Avenida Astrof\u00edsico Francisco S\u00e1nchez, 2, 38206 La Laguna, Tenerife, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones F\u00e1rmaco Bioqu\u00edmicas, Facultad de Ciencias Farmac\u00e9uticas y Bioqu\u00edmicas, Universidad Mayor de San Andr\u00e9s, Avenida Saavedra 2224, Miraflores, La Paz 00067, Bolivia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ninoska","family":"Flores","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones F\u00e1rmaco Bioqu\u00edmicas, Facultad de Ciencias Farmac\u00e9uticas y Bioqu\u00edmicas, Universidad Mayor de San Andr\u00e9s, Avenida Saavedra 2224, Miraflores, La Paz 00067, Bolivia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11101-010-9205-x","article-title":"Phenylphenalenone phytoalexins, will they be a new type of fungicide?","volume":"11","author":"Echeverri","year":"2012","journal-title":"Phytochem. 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