Bednarczyk-Cwynar Barbara, Ruszkowski Piotr
Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Collegium Pharmaceuticum 2 (CP.2), Rokietnicka Str. 3, 60-806 Poznan, Poland.
Center of Innovative Pharmaceutical Technology (CITF), Rokietnicka Str. 3, 60-806 Poznan, Poland.
Pharmaceutics. 2024 Jan 9;16(1):86. doi: 10.3390/pharmaceutics16010086.
(1) Background: The aim of the presented work was to obtain a set of oleanolic acid derivatives with a high level of anticancer activity and a low level of toxicity by applying an economic method. Three types of oleanolic acid derivatives were obtained: (i) derivatives of methyl oleanonate oxime, (ii) derivatives of methyl oleanonate oxime with an additional 11-oxo function, and (iii) derivatives of morpholide of oleanonic acid oxime. (2) Methods: The above oximes were acylated with aliphatic or aromatic carboxylic acid. The newly obtained compounds were subjected to ADMETox analysis and were also tested for cytotoxicity activity on the HeLa, KB, MCF-7, A-549, and HDF cell lines with the MTT assay. (3) Results: Among the tested acylated oximes of oleanolic acid, some derivatives, particularly those with two nitro groups attached to the aromatic ring, proved to be the most potent cytotoxic agents. These triterpene derivatives significantly inhibited the growth of the HeLa, KB, MCF-7, and A-549 cancer cell lines in micromolar concentrations. (4) Conclusions: The introduction of different moieties, particularly the 3,5-dinitro group, resulted in the synthesis of highly potent cytotoxic agents with favorable SI and ADMETox parameters.
(1) 背景：本研究的目的是通过一种经济的方法获得一组具有高抗癌活性和低毒性的齐墩果酸衍生物。得到了三种类型的齐墩果酸衍生物：(i) 齐墩果酸甲酯肟衍生物，(ii) 具有额外11-氧代功能的齐墩果酸甲酯肟衍生物，以及(iii) 齐墩果酸肟吗啉代衍生物。(2) 方法：上述肟与脂肪族或芳香族羧酸进行酰化反应。对新得到的化合物进行ADMETox分析，并通过MTT法检测其对HeLa、KB、MCF-7、A-549和HDF细胞系的细胞毒性活性。(3) 结果：在测试的齐墩果酸酰化肟中，一些衍生物，特别是那些芳香环上连接有两个硝基的衍生物，被证明是最有效的细胞毒性剂。这些三萜衍生物在微摩尔浓度下显著抑制HeLa、KB、MCF-7和A-549癌细胞系的生长。(4) 结论：引入不同的基团，特别是3,5-二硝基基团，导致合成了具有良好的SI和ADMETox参数的高效细胞毒性剂。
