2. Academic Validation
  3. Design, synthesis, and in vivo and in vitro biological screening of pseudolaric acid B derivatives as potential anti-tumor agents

Design, synthesis, and in vivo and in vitro biological screening of pseudolaric acid B derivatives as potential anti-tumor agents

  • Bioorg Chem. 2024 Jul 30:151:107670. doi: 10.1016/j.bioorg.2024.107670.
Qian Xu 1,  Hao Deng 1,  Xing Huang 1,  Jin-Ying Liu 1,  Guo-Qing Chen 1,  Qing-Kun Shen 1,  Zhe-Shan Quan 2,  Hong-Yan Guo 3,  Xiu-Mei Yin 4
Affiliations

Affiliations

  • 1 Key Laboratory of Natural Medicines of the Changbai Mountain, Affifiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China.
  • 2 Key Laboratory of Natural Medicines of the Changbai Mountain, Affifiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China. Electronic address: zsquan@ybu.edu.cn.
  • 3 Key Laboratory of Natural Medicines of the Changbai Mountain, Affifiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China. Electronic address: hongyanguo@ybu.edu.cn.
  • 4 Key Laboratory of Natural Medicines of the Changbai Mountain, Affifiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China. Electronic address: yinxm@ybu.edu.cn.
PMID: 39096560 DOI: 10.1016/j.bioorg.2024.107670
Abstract

Pseudolaric Acid B (PAB), a natural product with remarkable anti-tumor activity, is a starting point for new Anticancer therapeutics. We designed and synthesized 27 PAB derivatives and evaluated their anti-proliferative activities against four Cancer cell lines: MCF-7, HCT-116, HepG2, and A549. Compared with unmodified PAB, the PAB derivatives showed stronger anti-proliferative activity. The ability of compound D3 (IC50 = 0.21 μM) to inhibit HCT-116 cells was approximately 5.3 times that of PAB (IC50 = 1.11 μM) and the antiproliferative action was unrelated to cytotoxicity (SI=20.38), indicating its superior safety profile (PAB; SI=0.95). Compound D3 effectively suppressed the EdU-positive rate and reduced colony formation, arrested HCT-116 cells in the S and G2/M phases and induced Apoptosis. In vivo experiments further demonstrated low toxicity of compound D3 while suppressing tumor growth in mice. In summary, given its strong anti-proliferative effect and relative safety, further development of compound D3 is warranted.

Keywords

Apoptosis; Cell cycle; Pseudolaric Acid B; Structural modification.

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