Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Collegium Pharmaceuticum 2 (CP.2), Rokietnicka Str. 3, 60-806 Poznan, Poland.
Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznan University of Medical Sciences, Collegium Pharmaceuticum 1 (CP.1), Rokietnicka Str. 3, 60-806 Poznan, Poland.
Molecules. 2024 Jul 31;29(15):3623. doi: 10.3390/molecules29153623.
The presented work aimed to explore the potential of oleanolic acid dimers (OADs): their cytostatic and antioxidant activities, molecular docking, pharmacokinetics, and ADMETox profile. The cytostatic properties of oleanolic acid () and its 14 synthesised dimers (-) were evaluated against 10 tumour types and expressed as IC values. Molecular docking was performed with the CB-Dock2 server. Antioxidant properties were evaluated with the CUPRAC method. ADMETox properties were evaluated with the ADMETlab Manual (2.0) database. The results indicate that the obtained OADs can be effective cytostatic agents, for which the IC not exceeded 10.00 for many tested cancer cell lines. All OADs were much more active against all cell lines than the mother compound (). All dimers can inhibit the interaction between the 1MP8 protein and cellular proteins with the best results for compounds and with unsaturated bonds within the linker. An additional advantage of the tested OADs was a high level of antioxidant activity, with Trolox equivalent for OADs , , -, , and of approximately 0.04 mg/mL, and beneficial pharmacokinetics and ADMETox properties. The differences in the DPPH and CUPRAC assay results obtained for OADs may indicate that these compounds may be effective antioxidants against different radicals.
本工作旨在探索齐墩果酸二聚体（OAD）的潜力：其细胞增殖抑制和抗氧化活性、分子对接、药代动力学和 ADMETox 特性。用 IC 值评估齐墩果酸（）及其 14 个合成二聚体（-）对 10 种肿瘤类型的细胞增殖抑制作用。用 CB-Dock2 服务器进行分子对接。用 CUPRAC 法评估抗氧化活性。用 ADMETlab Manual（2.0）数据库评估 ADMETox 特性。结果表明，所得到的 OAD 可能是有效的细胞增殖抑制剂，其中许多测试的癌细胞系的 IC 不超过 10.00。所有 OAD 对所有细胞系的活性都高于母体化合物（）。所有二聚体都能抑制 1MP8 蛋白与细胞蛋白的相互作用，其中具有不饱和键的连接子的化合物和 具有最佳效果。测试的 OAD 的另一个优点是具有高抗氧化活性，OADs 、 、 、 、 的 Trolox 当量约为 0.04mg/ml，具有良好的药代动力学和 ADMETox 特性。OAD 在 DPPH 和 CUPRAC 测定中得到的结果差异可能表明，这些化合物可能是针对不同自由基的有效抗氧化剂。
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