Suárez Alírica Isabel, Chávez Katiuska, Garmendia Jenny Valentina, De Sanctis Claudia Valentina, Gurská Soňa, Džubák Petr, Hajduch Marian, De Sanctis Juan Bautista
Unidad de Investigación en Productos Naturales, Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1040, Venezuela.
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 779 00 Olomouc, Czech Republic.
Pharmaceuticals (Basel). 2025 Jul 15;18(7):1043. doi: 10.3390/ph18071043.
The natural compounds caracasine acid () and its methyl ester, caracasine (), isolated from the flowers of , are effective against several tumor cell lines. Five semi-synthetic derivatives (-) were synthesized based on these structures. The study aimed to evaluate the cytotoxic activity of these compounds in 2D and spheroid cultures. 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. : The parent compound (), the natural ester (), and two novel derivatives, the anhydride () and the cyclohexanol ester (), 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 ( < 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. These findings indicate potential applications in leukemia treatment, albeit with limited efficacy against solid tumors.
从**（此处原文缺失植物名称）**花中分离出的天然化合物加拉卡辛酸（）及其甲酯加拉卡辛（）对多种肿瘤细胞系有效。基于这些结构合成了五种半合成衍生物（-）。该研究旨在评估这些化合物在二维和球体培养中的细胞毒性活性。实验在一组12种人类细胞系中进行，包括8种癌细胞系和4种正常细胞系。对源自HCT116、HCT116 p53基因敲除（p53KO）、A549和U2OS细胞系的球体，以及包含肿瘤细胞和正常成纤维细胞的混合球体进行了化合物评估。结果表明：母体化合物（）、天然酯（）以及两种新型衍生物酸酐（）和环己醇酯（）在传统二维培养中对不同白血病细胞以及HCT116、HCT116 p53基因敲除（p53KO）、A549和U2OS细胞系表现出细胞毒性。然而，与其他肿瘤细胞系相比，二维培养中白血病细胞系中的过氧化物形成显著更高（<0.01）。这些化合物在球体培养中未诱导细胞死亡；处理后半胱天冬酶8、9和3未被激活。这些发现表明其在白血病治疗中有潜在应用，尽管对实体瘤的疗效有限。
