{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:20:38Z","timestamp":1785943238884,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Venezuelan Ministry of Science and Technology","award":["20230PGP99"],"award-info":[{"award-number":["20230PGP99"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: The natural compounds caracasine acid (1) and its methyl ester, caracasine (2), isolated from the flowers of Croton micans, are effective against several tumor cell lines. Five semi-synthetic derivatives (3\u20137) were synthesized based on these structures. The study aimed to evaluate the cytotoxic activity of these compounds in 2D and spheroid cultures. Methods: The assays were performed in a panel of 12 human cell lines, 8 cancer and 4 normal cell lines. The compounds were evaluated on spheroids derived from the HCT116, HCT116 p53 knockout (p53KO), A549, and U2OS cell lines, as well as mixed spheroids comprising tumor cells and normal fibroblasts. Results: The parent compound (1), the natural ester (2), and two novel derivatives, the anhydride (7) and the cyclohexanol ester (3), demonstrated cytotoxicity against different leukemic cells and HCT116, HCT116 p53 knockout (p53KO), A549, and U2OS cell lines in conventional two-dimensional cultures. Peroxide formation, however, was significantly higher in leukemic cell lines (p &lt; 0.01) in 2D culture as compared with the other tumor cell lines. The compounds did not induce cell death in spheroid cultures; caspases 8, 9, and 3 were not activated upon treatment. Conclusions: These findings indicate potential applications in leukemia treatment, albeit with limited efficacy against solid tumors.<\/jats:p>","DOI":"10.3390\/ph18071043","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T08:24:17Z","timestamp":1752654257000},"page":"1043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["New Derivatives of Caracasine Acid with Anti-Leukemic Activity and Limited Effectiveness in Spheroid Cultures"],"prefix":"10.3390","volume":"18","author":[{"given":"Al\u00edrica Isabel","family":"Su\u00e1rez","sequence":"first","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Productos Naturales, Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1040, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katiuska","family":"Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Productos Naturales, Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1040, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny Valentina","family":"Garmendia","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7864-7379","authenticated-orcid":false,"given":"Claudia Valentina","family":"De Sanctis","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So\u0148a","family":"Gursk\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-5969","authenticated-orcid":false,"given":"Petr","family":"D\u017eub\u00e1k","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic"},{"name":"Czech Advanced Technologies and Research Institute (CATRIN), Institute of Molecular and Translational Medicine, Palacky University, 779 00 Olomouc, Czech Republic"},{"name":"Laboratory of Experimental Medicine, University Hospital Olomouc, 779 00 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4834-908X","authenticated-orcid":false,"given":"Marian","family":"Hajduch","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic"},{"name":"Czech Advanced Technologies and Research Institute (CATRIN), Institute of Molecular and Translational Medicine, Palacky University, 779 00 Olomouc, Czech Republic"},{"name":"Laboratory of Experimental Medicine, University Hospital Olomouc, 779 00 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5480-4608","authenticated-orcid":false,"given":"Juan Bautista","family":"De Sanctis","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic"},{"name":"Czech Advanced Technologies and Research Institute (CATRIN), Institute of Molecular and Translational Medicine, Palacky University, 779 00 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100746","DOI":"10.1016\/j.phyplu.2025.100746","article-title":"The Croton genus (Euphorbiaceae) and its richness in chemical constituents with a potential range of applications","volume":"5","author":"Galvis","year":"2025","journal-title":"Phytomed. 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