Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
Steroids. 2023 Nov;199:109290. doi: 10.1016/j.steroids.2023.109290. Epub 2023 Aug 6.
In this study, we synthesized androsta-4,14-diene-3,16-dione, 12β-hydroxyandrosta-4,14-diene-3,16-dione, and other 3,16-androstenedione derivatives from commercially available dehydroepiandrosterone as a starting material in 9-13 steps with high yields. The bioactivity of the obtained compounds was evaluated. Compounds 14a and 23a were shown to have high antitumor activity against acute lymphoblastic leukemia cell lines Nalm-6 and BALL-1, respectively. Network pharmacology analysis showed that the anti-leukemia activity of compounds 14a and 23a might be related to the JAK2, ABL1 protein, and PI3K/Akt signaling pathways. The molecular docking of compounds 14a and 23a identified possible active sites, with the lowest docking scores for PTGS2 and MAPK14, respectively. In addition, the absorption, distribution, metabolism, and excretion prediction results revealed the drug-likeness of the two compounds. Therefore, compounds 14a and 23a should be considered anti-leukemia candidates in future studies.
在这项研究中，我们以商购的脱氢表雄酮为起始原料，经 9-13 步反应以较高产率合成了雄甾-4,14-二烯-3,16-二酮、12β-羟基雄甾-4,14-二烯-3,16-二酮等 3,16-雄烯二酮衍生物，并对所得化合物的生物活性进行了评价。结果表明，化合物 14a 和 23a 对急性淋巴细胞白血病细胞系 Nalm-6 和 BALL-1 具有较高的抗肿瘤活性。网络药理学分析表明，化合物 14a 和 23a 的抗白血病活性可能与 JAK2、ABL1 蛋白和 PI3K/Akt 信号通路有关。化合物 14a 和 23a 的分子对接确定了可能的活性位点，其对接评分最低的分别为 PTGS2 和 MAPK14。此外，吸收、分布、代谢和排泄预测结果表明了这两个化合物的类药性。因此，化合物 14a 和 23a 应在未来的研究中被视为抗白血病候选物。
