Scholarlink

<p>Cancer is the second leading cause of death worldwide, highlighting the urgent need for novel therapeutic strategies and targeted drug development. Oleanolic acid (OA) is a natural compound with notable antitumor activity. This study aimed to develop OA derivatives with enhanced antitumor potency through structural optimization and biological evaluation. First, modifications were introduced at the C28 carboxylic acid group of OA to generate a series of acylhydrazone derivatives. Their structures were confirmed via ¹H NMR, <sup>13</sup>C NMR, HRMS, and X-ray single-crystal diffraction. Subsequently, the cytotoxic effects of these derivatives were assessed in tumor cell lines (A549, AGS, and K562) using the CCK-8 assay, with cisplatin as a positive control. Notably, compounds <b>5</b>, <b>6</b>, <b>9</b>, <b>10</b>, <b>16</b>, <b>21</b>, <b>27</b>, and <b>28</b> showed stronger inhibitory activity than cisplatin. Among them, compound <b>28</b> exhibited the highest potency against A549 (IC<sub>50</sub> = 8.34 ± 0.65 µM) and K562 cells (IC<sub>50</sub> = 6.25 ± 0.57 µM), while derivative <b>16</b> showed the best efficacy against AGS cells (IC<sub>50</sub> = 7.93 ± 0.81 µM). Finally, network pharmacology analysis was performed to identify the core signaling pathways and targets of compound <b>16</b> in AGS cells and compound <b>28</b> in A549 and K562 cells. Six key proteins (SRC, PLCG1, EGFR, GRB2, IL1B, and HSP90AB1) with high degree values (&gt; 10) were identified. Molecular docking further confirmed strong binding interactions—mainly hydrogen bonds, π–π stacking, and other forces—between the active compounds and their targets. Collectively, this study offers valuable insights into the development of OA-based antitumor agents and highlights promising lead compounds for further investigation.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Synthesis and antitumor evaluation of oleanolic acid acylhydrazone derivatives

  • 期刊论文

  • 发表日期：

    2025年11月1日

查看全文
  • Juan Cai,
  • Bo-Wen Pan,
  • Liang-Liang Zheng,
  • You-Ping Tian,
  • Zhang-Chao Dong,
  • Li-Juan Liu,
  • Ting-Ting Feng,
  • Ying Zhou,
  • Xiong-Wei Liu,
  • Yang Shi

摘要

Cancer is the second leading cause of death worldwide, highlighting the urgent need for novel therapeutic strategies and targeted drug development. Oleanolic acid (OA) is a natural compound with notable antitumor activity. This study aimed to develop OA derivatives with enhanced antitumor potency through structural optimization and biological evaluation. First, modifications were introduced at the C28 carboxylic acid group of OA to generate a series of acylhydrazone derivatives. Their structures were confirmed via ¹H NMR, 13C NMR, HRMS, and X-ray single-crystal diffraction. Subsequently, the cytotoxic effects of these derivatives were assessed in tumor cell lines (A549, AGS, and K562) using the CCK-8 assay, with cisplatin as a positive control. Notably, compounds 5, 6, 9, 10, 16, 21, 27, and 28 showed stronger inhibitory activity than cisplatin. Among them, compound 28 exhibited the highest potency against A549 (IC50 = 8.34 ± 0.65 µM) and K562 cells (IC50 = 6.25 ± 0.57 µM), while derivative 16 showed the best efficacy against AGS cells (IC50 = 7.93 ± 0.81 µM). Finally, network pharmacology analysis was performed to identify the core signaling pathways and targets of compound 16 in AGS cells and compound 28 in A549 and K562 cells. Six key proteins (SRC, PLCG1, EGFR, GRB2, IL1B, and HSP90AB1) with high degree values (> 10) were identified. Molecular docking further confirmed strong binding interactions—mainly hydrogen bonds, π–π stacking, and other forces—between the active compounds and their targets. Collectively, this study offers valuable insights into the development of OA-based antitumor agents and highlights promising lead compounds for further investigation.

Graphical abstract