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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F25%3A10159337" target="_blank" >RIV/00098892:_____/25:10159337 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/1424-8247/18/7/1043" target="_blank" >https://www.mdpi.com/1424-8247/18/7/1043</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ph18071043" target="_blank" >10.3390/ph18071043</a>

Result language

angličtina

Original language name

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

Original language description

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 &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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Pharmaceuticals

ISSN

—

e-ISSN

1424-8247

Volume of the periodical

18

Issue of the periodical within the volume

7

Country of publishing house

CH - SWITZERLAND

Number of pages

19

Pages from-to

1043

UT code for WoS article

001541094600001

EID of the result in the Scopus database

2-s2.0-105011684245