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Volume 18
Issue 7
10.3390/ph18071043
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Article

New Derivatives of Caracasine Acid with Anti-Leukemic Activity and Limited Effectiveness in Spheroid Cultures

by
Alírica Isabel Suárez
1,*,
Katiuska Chávez
1,
Jenny Valentina Garmendia
2,
Claudia Valentina De Sanctis
2,
Soňa Gurská
2,
Petr Džubák
2,3,4,
Marian Hajduch
2,3,4 and
Juan Bautista De Sanctis
2,3,*
1
Unidad de Investigación en Productos Naturales, Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1040, Venezuela
2
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic
3
Czech Advanced Technologies and Research Institute (CATRIN), Institute of Molecular and Translational Medicine, Palacky University, 779 00 Olomouc, Czech Republic
4
Laboratory of Experimental Medicine, University Hospital Olomouc, 779 00 Olomouc, Czech Republic
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(7), 1043; https://doi.org/10.3390/ph18071043
Submission received: 13 June 2025 / Revised: 9 July 2025 / Accepted: 14 July 2025 / Published: 15 July 2025
(This article belongs to the Special Issue Recent Advances in the Discovery and Development of Drugs for Civilization Diseases, 2nd Edition)
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Abstract

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 (3–7) 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 < 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.
Keywords: caracasine acid derivatives; cytotoxicity; leukemia; spheroids caracasine acid derivatives; cytotoxicity; leukemia; spheroids

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MDPI and ACS Style

Suárez, A.I.; Chávez, K.; Garmendia, J.V.; De Sanctis, C.V.; Gurská, S.; Džubák, P.; Hajduch, M.; De Sanctis, J.B. New Derivatives of Caracasine Acid with Anti-Leukemic Activity and Limited Effectiveness in Spheroid Cultures. Pharmaceuticals 2025, 18, 1043. https://doi.org/10.3390/ph18071043

AMA Style

Suárez AI, Chávez K, Garmendia JV, De Sanctis CV, Gurská S, Džubák P, Hajduch M, De Sanctis JB. New Derivatives of Caracasine Acid with Anti-Leukemic Activity and Limited Effectiveness in Spheroid Cultures. Pharmaceuticals. 2025; 18(7):1043. https://doi.org/10.3390/ph18071043

Chicago/Turabian Style

Suárez, Alírica Isabel, Katiuska Chávez, Jenny Valentina Garmendia, Claudia Valentina De Sanctis, Soňa Gurská, Petr Džubák, Marian Hajduch, and Juan Bautista De Sanctis. 2025. "New Derivatives of Caracasine Acid with Anti-Leukemic Activity and Limited Effectiveness in Spheroid Cultures" Pharmaceuticals 18, no. 7: 1043. https://doi.org/10.3390/ph18071043

APA Style

Suárez, A. I., Chávez, K., Garmendia, J. V., De Sanctis, C. V., Gurská, S., Džubák, P., Hajduch, M., & De Sanctis, J. B. (2025). New Derivatives of Caracasine Acid with Anti-Leukemic Activity and Limited Effectiveness in Spheroid Cultures. Pharmaceuticals, 18(7), 1043. https://doi.org/10.3390/ph18071043

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